Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study re...Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using MOE (Molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. Moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.展开更多
Objective: To investigate and compare the antileishmanial effects of CAPE and(CAPE)PLGA NPs on Leishmania infantum(L.infantum) promastigotes and amastigotes in vitro,Methods: Efficacies of CAPE,(CAPE)PLGA NPs and free...Objective: To investigate and compare the antileishmanial effects of CAPE and(CAPE)PLGA NPs on Leishmania infantum(L.infantum) promastigotes and amastigotes in vitro,Methods: Efficacies of CAPE,(CAPE)PLGA NPs and free PLGA nanoparticles(NPs) on promastigotes were evaluated using MTT and promastigote count assays,and their anti-amastigote effects were determined via infection index analysis,Griess reaction was also performed to calculate nitric oxide production of macrophages exposed to investigated molecules,Results: It was determined that CAPE and(CAPE)PLGA NPs demonstrated significant inhibitory effects on L.infantum promastigotes and amastigotes,while free NPs did not exhibit any meaningful antileishmanial effectiveness,The IC50 values of CAPE for L.infantum promastigotes and amastigotes were assessed as(51.0±0.8) and(19.0±1.4) μg/m L,respectively(P<0.05),On the other side,it was revealed that(CAPE)PLGA NPs had superior antileishmanial activity on both forms of parasites since its IC50 values for L.infantum promastigotes and amastigotes were(32.0±1.3) and(8.0±0.9) μg/m L,respectively(P<0.05),It was also determined that both agents strongly stimulated nitric oxide production of macrophages,Conclusions: The obtained results show that(CAPE)PLGA NPs have a great potential to be especially used in treatment of visceral leishmaniasis; however,in vivo antileishmanial screening of these molecules should be performed in the near future.展开更多
A series of novel azasterols 8a―8h and 10a―10c were synthesized from the key intermediate 6 by acylation and deprotection.Compound 6 was obtained through a series of reactions including Wittig reaction,etherificatio...A series of novel azasterols 8a―8h and 10a―10c were synthesized from the key intermediate 6 by acylation and deprotection.Compound 6 was obtained through a series of reactions including Wittig reaction,etherification,ene reaction,oxidation,oximation and reduction.Structures of the synthesized compounds were confirmed by IR,MS and 1H NMR.Furthermore,all of these compounds were screened for in vitro antiparasitic activity against L.donovani.Among them,compounds 8h,10a and 10b showed a fair inhibition of leishmania promastigotes growth at 25 μg/mL,with potencies close to that of the reference drug,amphotericin B.The results provide a starting point for the development of novel drugs to treat leishmaniasis.展开更多
Melodinus eugeniifolus, a very rare medical plant which belongs to the family of Apocynaceae, has just been discovered in the Malaysia rain forest. Six different extracts of Melodinus eugeniifolus (a very rare medical...Melodinus eugeniifolus, a very rare medical plant which belongs to the family of Apocynaceae, has just been discovered in the Malaysia rain forest. Six different extracts of Melodinus eugeniifolus (a very rare medical plant belongs to Apocynaceae) leaves and barks were screened for the in vitro antileishmanial and antibacterial activities, among the different extracts tested, the ethanol and hexane extract of barks showed significant antileishmanial activities with IC50 value of 159.9 μg/ml and 270.3 μg/ml. All the extracts displayed remarkable antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Highlights: Melodinus eugeniifolus, a very rare medical plant from South Asian rain forest which may be a potential drug for many diseases is first reported its antileishmanial and antimicrobial activities.展开更多
Visceral leishmaniasis (VL) is a pestilent form of leishmaniasis that chiefly impinges the poorest sections of the society. The prototypical therapeutic interventions in vogue are handicapped due to toxicity and alarm...Visceral leishmaniasis (VL) is a pestilent form of leishmaniasis that chiefly impinges the poorest sections of the society. The prototypical therapeutic interventions in vogue are handicapped due to toxicity and alarming increase in drug resistance. In the absence of vaccines, progressive emergence of HIV-VL co-infection and relapse in the form of post kala-azar dermal leishmaniasis, have fuelled the quest for alternative therapies. Herein, we report antileishmanial activity of Piper nigrum, which is endowed with multifarous medicinal properties. Hexane (PNH) and ethanolic (PNE) extracts of P. nigrum substantially inhibited the growth of Leishmania donovani promastigotes with 50% inhibitory concentration (IC50) of 31.6 and 37.8 μg·ml-1, respectively. Growth reversibility analysis revealed the leishmanicidal effect of PNH which caused cell shrinkage and flagellar disruption. In contrast, PNE treated promastigotes showed partial effect. PNH and PNE also abrogated the growth of intra-macrophagic Leishmania amastigotes with IC50 of 14.6 and 18.3 μg·ml-1, respectively. Anti-amastigote efficacy of PNH was accompanied by higher selectivity over host macrophages than PNE. Gas-Chromatography-Mass Spectrometry showed the presence of several secondary metabolites such as trans-β-caryophyllene, piperine, β-bisabolene and other sesquiterpenes in PNH and piperine, δ-(sup 9)-cis oleic acid and piperyline in PNE. Conclusively, our work revealed discernible antileishmanial activity of P. nigrum extracts.展开更多
Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utiliti...Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utilities in traditional medicine. Materials and Methods: The methanol extract of K. africana fruits was subjected to chromatographic fractionation utilizing different techniques. The methanol extract together with the isolated compounds were tested for their bioactivities in a series of cell-based assays. Results: The current work led to isolation and characterization of nine constituents including iridoid glycosides, phenylpropanoid derivatives, and a eucommiol derivative. The hexanes extract caused inhibition of the opportunistic yeast; Cryptococcus neoformans Pinh. The chloroform extract exhibited substantial antileishmanial activity of Leishmania donovani. Verminoside(1) showed weak inhibition of the CB1, CB2, and Kappa opioid receptors. Compound 4 exhibited weak inhibition of the Kappa and Mu opioid receptors. The hexanes and the chloroform extracts of K. africana exhibited inhibitory activity against the pathogenic parasite Trypanosoma brucei. The ethyl acetate extract showed the same activity. Conclusions: This is the first report on the isolation of coniferyl 4-0-(3-D-glucopyranoside(7), a eucommiol derivative(crescentin IV)(6), and 6-feruloylcatalpol(4) from the genus Kigelia. It is also the first report on the separation of ajugol(2), catalpol(3), and specioside(5) from the fruits of K. africana. Revision of the^1 H and ^(13)C-NMR spectra of 6-feruloylcatalop(4) and 6-p-hydroxycinnamoylcatalpol(5, specioside) is described. Further, the results of the in vitro assays corroborate the traditional utility of this plant in medicine.展开更多
Objective:To investigate two cyanobacteria isolated from different origins i.e.Lyngbya aestuarii(L.aestuarii)from brackish water and Aphanothece bullosa(4.bullosa)from fresh water paddy fields for antifungal and antil...Objective:To investigate two cyanobacteria isolated from different origins i.e.Lyngbya aestuarii(L.aestuarii)from brackish water and Aphanothece bullosa(4.bullosa)from fresh water paddy fields for antifungal and antileishmanila activity taking Candida albicans and Leishmania donovain as targets.Methods:Biomass of L.aestuarii and A.bullosa were harvested after 40 and60 d respectively and lyophilized twice in methanol(100%)and redissolved in methanol(5%)for bioassay.Antifungal bioassay was done by agar well diffusion method while antileishmanial,by counting cell numbers and flageller motility observation of promastigotes and amastigotes from L.donovani.fluconazole and 5%methanol were used as control.Results:Both the cyanobacteria were found to be potent source of antifungal activity keeping fluconazole as positive control,however,methanolic crude extract(15 mg/mL)of A.bullosa was found more potent(larger inhibition zone)over that of methanolic crude extract of L.aestuarii,Similarly antileishmanial activity of crude extract(24.0 mg/mL)of A.bullosa was superior over that of methanolic crude extract of L.aestuarii(25.6 mg/mL).Conclusions:Antifungal and antileishmanial drugs are still limited in the market.Screening of microbes possessing antifungal and antileishmanial activity drug is of prime importance.Cyanobacteria are little explored in this context because most of the drugs in human therapy are derived from microorganisms,mainly bacterial,fungal and actinomycetes.Thus in the present study two cyanobacterial strains from different origins showed potent source of antifungal and antileishmanial biomolecules.展开更多
A series of novel 3-substituted-4-hydroxycoumarin derivatives 6（a-1） were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated...A series of novel 3-substituted-4-hydroxycoumarin derivatives 6（a-1） were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity（DPPH-radical scavenging activity）. Two compounds, 6h（IC50= 9.90 μmol/L） and 6i（IC50= 6.90 μmol/L） displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine（IC50= 16.15 μmol/L） and miltefosine（IC50= 12.50 μmol/L）. Three compounds, 6c（IC50= 10.79 μmol/L）, 6h（IC50= 10.60 μmol/L）, and 6i（IC50= 10.73 μmol/L） showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene（IC50= 16.47 μmol/L） and ascorbic acid（IC50= 12.69 μmol/L）. A molecular docking study of compounds 6（a-1） suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L.donovani. ADME properties were predicted in silico and support the potential of 6（a-1） to show favorable drug-like properties.展开更多
OBJECTIVE:To collect and screen for ethnopharmacological properties(antileishmanial,antibacterial and brine lethality assays) of medicinal plant Ocimum basilicum from Peshawar region(34.008 latitude and 71.57 altitude...OBJECTIVE:To collect and screen for ethnopharmacological properties(antileishmanial,antibacterial and brine lethality assays) of medicinal plant Ocimum basilicum from Peshawar region(34.008 latitude and 71.57 altitudes).METHODS:In the present study a general antileishmanial activity against Leishmania tropica strain was carried out.The antibacterial potential of the plant was performed against 06 gram positive and 06 gram negative bacteria.Brine shrimp cytotoxicity assay at different concentrations were investigated.RESULTS:The anti-promastigotes profile of the plant showed good antileishmanial activity exhibited LC_(50) value 21.67 μg/mL.The result for gram positive antibacterial activity revealed that the O.basilicum leaves extract possesses significant inhibitory activity at highest two concentrations ranging from20.66 ± 0.31 to 31.86 ± 0.80 for Clostridium perfringens type C and Bacillus subtitilis,respectively,as compared to the gentamycin(27.36 ± 0.55 and21.80 ± 0.72,respectively).For gram negative bacteria good activity was observed.A highest zone of inhibition was recorded for Pseudomonas aeroginosa(28.83 ± 0.28) atthe highest concentration(10 mg/mL).The LC_(50) value obtained for brine shrimp lethality assay was 91.56 μg/mL.CONCLUSION:The herb basil possesses effective cidal activities which make this plant a good candidate for the isolation of antiprotozoal and antibacterial compounds which may lead to the development of novel drug.展开更多
Objective:To investigate the biochemical capacity,and in vitro inhibitory effects of hairy roots from two cultivars of Ficus carica L.(Sabz and Siah)on Leishmania major promastigotes and amastigotes.Methods:In the hai...Objective:To investigate the biochemical capacity,and in vitro inhibitory effects of hairy roots from two cultivars of Ficus carica L.(Sabz and Siah)on Leishmania major promastigotes and amastigotes.Methods:In the hairy roots,the activity of antioxidant enzymes compared to normal leaves and roots,and the presence of some phenolic compounds in comparison with fruits were investigated.The IC_(50) values of hairy roots in promastigotes was determined by tetrazolium-dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays.By calculating the infectivity index of peripheral blood mononuclear cells(PBMCs),the leishmanicidal activity(IC_(50) values)of hairy roots for amastigotes was estimated.The effects of hairy roots(IC_(50) values)treatment on the levels of IFN-γ and iNOS expression,intracellular reactive oxygen species,and iNOS protein expression in infected-PBMCs were determined.Results:Based on antioxidant enzyme assays and high performance liquid chromatography analysis,hairy roots exhibited high antioxidant capacity and contained high levels of phenolic compounds.According to the results of tetrazolium-dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays,the hairy root extracts of both cultivars showed considerable dose-dependent inhibitory effects against Leishmania major promastigotes.Depending on the concentration and exposure time,treatment of infected-PBMCs with hairy root extracts caused the generation of a significant reactive oxygen species,up-regulation of IFN-γ and iNOS genes expression,and high value of iNOS protein compared to controls.Conclusions:The findings of this study suggest that the hairy roots of Ficus carica can be considered as a promising natural source of antileishmanial agents.展开更多
To study the phytochemical constituents and in vitro biological activities of hydromethanolic extract and fractions from Algerian Sahara Myrtus nivellei (M. nivellei) collected in Hoggar region and to identify th...To study the phytochemical constituents and in vitro biological activities of hydromethanolic extract and fractions from Algerian Sahara Myrtus nivellei (M. nivellei) collected in Hoggar region and to identify the active fraction that can act as an alternative of commonly used antibiotics and as antileishmanial or antioxidant agents.MethodsPhytochemical screening of M. nivellei aerial parts was realised according to the literature. Extract was firstly prepared by using aqueous methanol then fractionated with ethyl acetate and butanol solvents. Total phenolics, tannis and flavonoids, of the hydromethanolic extract and their fractions were determined by Folin-Ciocalteu method as gallic acid equivalents and by aluminium chloride as rutin equivalent respectively. Extract and fractions were tested for their antimicrobial and antiparasital activities against standard bacteria using agar diffusion method and two kinds of leishmania visceral and cutaneous. The antioxidant activities were realized using phosphomolybdenum, FRAP and DPPH tests.ResultsPreliminary phytochemical screening exhibited the presence of flavonoids, tannins, saponins, and alkaloids. The experimental results showed that plant extract and fractions were high in phenolic compounds and exhibited an important role as antioxidant, antimicrobial and had a moderate antileishmanial activity.ConclusionsThese observations lead us toward more studies in this field, so that we can get more benefits from our local Algerian medicinal plants.展开更多
Objective:To investigate the seeds of Millettia ferruginea(M.ferruginea)to unravel its antibacterial,antifungal,antitubercular,and antileishmanial potential for the first time.Methods:M.ferruginea seeds were refluxed ...Objective:To investigate the seeds of Millettia ferruginea(M.ferruginea)to unravel its antibacterial,antifungal,antitubercular,and antileishmanial potential for the first time.Methods:M.ferruginea seeds were refluxed separately with chloroform,methanol and water to prepare the three extracts,which were tested against the reference strains of Gram-positive and Gram-negative bacteria,yeast cells,Mycobacterium tuberculosis and Leishmania donovani(L.donovani)promastigotes.Next,the seeds were chemically analysed to isolate three constituent compounds,viz.,barbigerone,calopogonium isoflavone-A and durmillone,which were purified,characterised and evaluated for antibacterial and antileishmanial activity.Further,Comet assay was conducted to observe DNA fragmentation effects on human peripheral blood mononuclear cells pretreated with the isoflavonoid compounds.Results:The chloroform and methanol extracts of M.ferruginea seeds exhibited antibacterial and antileishmanial activity.The pure compounds also showed inhibitory activity against Gram-negative ATCC strains(minimum inhibitory concentration~0.5μmol/L),and L.donovani promastigotes(IC_(50)8.2-87.3μg/mL).However,they had little or no activity against yeast cells and tubercle bacilli.The DNA fragmentation study showed that the isoflavonoid constituents of M.ferruginea seeds were safe at therapeutic doses.Conclusions:The antibacterial efficacy of the non-aqueous extracts of M.ferruginea seed was observed against both Gram-positive and Gram-negative ATCC strains.Moreover,the constituents isoflavonoids,viz.,barbigerone,calopogonium isoflavone-A and durmillone,exhibited inhibitory activity against Gram-negative ATCC strains and L.donovani promastigotes.The comet assay showed that the compounds were safe to be considered for human consumption.展开更多
The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs th...The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.展开更多
Background:Adverse effects of antileishmanial drugs can affect patients’quality of life and adherence to therapy for visceral leishmaniasis(VL)and post-kala-azar dermal leishmaniasis(PKDL).In Bangladesh,there are 26 ...Background:Adverse effects of antileishmanial drugs can affect patients’quality of life and adherence to therapy for visceral leishmaniasis(VL)and post-kala-azar dermal leishmaniasis(PKDL).In Bangladesh,there are 26 treatment centers that manage leishmaniasis cases coming from 100 endemic upazilas(subdistricts)of 26 districts(these include VL,PKDL,treatment failure,and relapse VL and cutaneous leishmaniasis cases).This study aimed to investigate the feasibility of using focused pharmacovigilance for VL(VLPV)in Bangladesh’s National Kala-azar Elimination Programme for the early detection and prevention of expected and unexpected adverse drug reactions(ADRs).Methods:This activity has been going on since December 2014.Activity area includes secondary public hospital or Upazila health complex(UHC)in hundred sub districts and Surya Kanta Kala-azar Research Center(SKKRC)in Mymensingh District,a specialized center for management of complicated VL and PKDL cases.Communicable Disease Control(CDC)of the Directorate General of Health Services(DGHS)assigned twenty five of hundred UHCs and SKKRC(total 26)as treatment centers depending on their suitable geographical location.This was implemented for better management of VL cases with Liposomal Amphotericin B(AmBisome®)to ensure patient convenience and proper utilization of this expensive donated drug.A VLPV expert committee and a UHC VLPV team were established,an operational manual and pharmacovigilance report forms were developed,training and refresher training of health personnel took place at UHCs and at the central level,collected information such as patient data including demographics,treatment history and response,adverse events were analyzed.This report includes information for the period from December 2014 to December 2016.Results:From December 2014 to December 2016,1327 leishmaniasis patients were treated and 1066(80%)were available for VLPV.Out of these,57,33,9,and 1%were new VL,PKDL,VL relapse,and other cases,respectively.Liposomal amphotericin B was mostly use展开更多
Objective:Current therapy strategies of leishmaniasis have some problems such as high cost,toxicity and side effects.Plant extracts can be a source of drugs to control leishmaniasis.In this study,the effect of hydroal...Objective:Current therapy strategies of leishmaniasis have some problems such as high cost,toxicity and side effects.Plant extracts can be a source of drugs to control leishmaniasis.In this study,the effect of hydroalcoholic and chloroformic extracts of Vigna radiata,Tamarix ramosissima,and Carthamus lanatus on Leishmania major and L.tropica was studied.Methods:The plant samples were collected from west of Iran and their extracts were prepared.Antipromastigote activity assay of all extracts was done using tetrazolium-dye assay.Results:Only high concentrations of V.radiata and C.lanatus were able to inhibit Leishmania,while both high and low concentrations of T.ramosissima had antileishmanial effect.No difference was observed between hydroalcoholic with chloroformic extract of each plant.Conclusion:Altogether,the results revealed the antileishmanial activity of T.ramosissima extracts against L.major and L.tropica,indicating its potential as an antileishmanial agent.展开更多
Objective:To evaluate the antileishmanial activity of a marine spongeHaliclona oculata.Methods:The crude methanol extract was prepared from the freshly collected sponge and its three fractions were also prepared by ma...Objective:To evaluate the antileishmanial activity of a marine spongeHaliclona oculata.Methods:The crude methanol extract was prepared from the freshly collected sponge and its three fractions were also prepared by maceration method.The antileishmanial activity of these extract and fractions was tested againstLeishmania donovani.Results:The antileishmanial activity was tested bothin vitroand in vivo.The crude methanol extract exerted almost complete inhibition of promastigotes(81.0%±6.9%)and 78.8%±5.2%inhibition of intracellular amastigotes at 100μg/mL with IC_(50)values of 29.5μg/mL and 40.6μg/mL,respectively.The treatment of 500 mg/kg(p.o.)of the crude methanol extract for 5 d for Leishmania donovani infected hamsters resulted in 78.35%±10.20%inhibition of intracellular amastigotes.At a lower dose(250 mg/kg),it exhibited poor efficacy.Among the fractions,highestin vitro(>75%)and in vivo(84.3%±10.2%)antileishmanial activity was observed in n-chloroform fraction with IC_(50)values of 54.2μg/mL and 61μg/mL against promastigotes and intracellular amastigotes,respectively.Hexane fraction andn-butanol(both insoluble and soluble)fractions were found inactivein vitroand in vivo.Conclusions:Our findings indicate that this marine sponge has the potential to provide new insight toward development of an effective antileishmanial agent and,hence,more exhaustive studies are needed for exploiting the vast marine resources of the world to combat the scourge of several parasitic diseases.展开更多
文摘Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using MOE (Molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. Moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.
基金supported by Yildiz Technical University Scientific Research Projects Coordination Department with Project NO.2014-07-04-GEP02
文摘Objective: To investigate and compare the antileishmanial effects of CAPE and(CAPE)PLGA NPs on Leishmania infantum(L.infantum) promastigotes and amastigotes in vitro,Methods: Efficacies of CAPE,(CAPE)PLGA NPs and free PLGA nanoparticles(NPs) on promastigotes were evaluated using MTT and promastigote count assays,and their anti-amastigote effects were determined via infection index analysis,Griess reaction was also performed to calculate nitric oxide production of macrophages exposed to investigated molecules,Results: It was determined that CAPE and(CAPE)PLGA NPs demonstrated significant inhibitory effects on L.infantum promastigotes and amastigotes,while free NPs did not exhibit any meaningful antileishmanial effectiveness,The IC50 values of CAPE for L.infantum promastigotes and amastigotes were assessed as(51.0±0.8) and(19.0±1.4) μg/m L,respectively(P<0.05),On the other side,it was revealed that(CAPE)PLGA NPs had superior antileishmanial activity on both forms of parasites since its IC50 values for L.infantum promastigotes and amastigotes were(32.0±1.3) and(8.0±0.9) μg/m L,respectively(P<0.05),It was also determined that both agents strongly stimulated nitric oxide production of macrophages,Conclusions: The obtained results show that(CAPE)PLGA NPs have a great potential to be especially used in treatment of visceral leishmaniasis; however,in vivo antileishmanial screening of these molecules should be performed in the near future.
基金Supported by the National Natural Science Foundation of China(No.20576094)
文摘A series of novel azasterols 8a―8h and 10a―10c were synthesized from the key intermediate 6 by acylation and deprotection.Compound 6 was obtained through a series of reactions including Wittig reaction,etherification,ene reaction,oxidation,oximation and reduction.Structures of the synthesized compounds were confirmed by IR,MS and 1H NMR.Furthermore,all of these compounds were screened for in vitro antiparasitic activity against L.donovani.Among them,compounds 8h,10a and 10b showed a fair inhibition of leishmania promastigotes growth at 25 μg/mL,with potencies close to that of the reference drug,amphotericin B.The results provide a starting point for the development of novel drugs to treat leishmaniasis.
文摘Melodinus eugeniifolus, a very rare medical plant which belongs to the family of Apocynaceae, has just been discovered in the Malaysia rain forest. Six different extracts of Melodinus eugeniifolus (a very rare medical plant belongs to Apocynaceae) leaves and barks were screened for the in vitro antileishmanial and antibacterial activities, among the different extracts tested, the ethanol and hexane extract of barks showed significant antileishmanial activities with IC50 value of 159.9 μg/ml and 270.3 μg/ml. All the extracts displayed remarkable antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Highlights: Melodinus eugeniifolus, a very rare medical plant from South Asian rain forest which may be a potential drug for many diseases is first reported its antileishmanial and antimicrobial activities.
文摘Visceral leishmaniasis (VL) is a pestilent form of leishmaniasis that chiefly impinges the poorest sections of the society. The prototypical therapeutic interventions in vogue are handicapped due to toxicity and alarming increase in drug resistance. In the absence of vaccines, progressive emergence of HIV-VL co-infection and relapse in the form of post kala-azar dermal leishmaniasis, have fuelled the quest for alternative therapies. Herein, we report antileishmanial activity of Piper nigrum, which is endowed with multifarous medicinal properties. Hexane (PNH) and ethanolic (PNE) extracts of P. nigrum substantially inhibited the growth of Leishmania donovani promastigotes with 50% inhibitory concentration (IC50) of 31.6 and 37.8 μg·ml-1, respectively. Growth reversibility analysis revealed the leishmanicidal effect of PNH which caused cell shrinkage and flagellar disruption. In contrast, PNE treated promastigotes showed partial effect. PNH and PNE also abrogated the growth of intra-macrophagic Leishmania amastigotes with IC50 of 14.6 and 18.3 μg·ml-1, respectively. Anti-amastigote efficacy of PNH was accompanied by higher selectivity over host macrophages than PNE. Gas-Chromatography-Mass Spectrometry showed the presence of several secondary metabolites such as trans-β-caryophyllene, piperine, β-bisabolene and other sesquiterpenes in PNH and piperine, δ-(sup 9)-cis oleic acid and piperyline in PNE. Conclusively, our work revealed discernible antileishmanial activity of P. nigrum extracts.
文摘Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utilities in traditional medicine. Materials and Methods: The methanol extract of K. africana fruits was subjected to chromatographic fractionation utilizing different techniques. The methanol extract together with the isolated compounds were tested for their bioactivities in a series of cell-based assays. Results: The current work led to isolation and characterization of nine constituents including iridoid glycosides, phenylpropanoid derivatives, and a eucommiol derivative. The hexanes extract caused inhibition of the opportunistic yeast; Cryptococcus neoformans Pinh. The chloroform extract exhibited substantial antileishmanial activity of Leishmania donovani. Verminoside(1) showed weak inhibition of the CB1, CB2, and Kappa opioid receptors. Compound 4 exhibited weak inhibition of the Kappa and Mu opioid receptors. The hexanes and the chloroform extracts of K. africana exhibited inhibitory activity against the pathogenic parasite Trypanosoma brucei. The ethyl acetate extract showed the same activity. Conclusions: This is the first report on the isolation of coniferyl 4-0-(3-D-glucopyranoside(7), a eucommiol derivative(crescentin IV)(6), and 6-feruloylcatalpol(4) from the genus Kigelia. It is also the first report on the separation of ajugol(2), catalpol(3), and specioside(5) from the fruits of K. africana. Revision of the^1 H and ^(13)C-NMR spectra of 6-feruloylcatalop(4) and 6-p-hydroxycinnamoylcatalpol(5, specioside) is described. Further, the results of the in vitro assays corroborate the traditional utility of this plant in medicine.
基金Supported by UGC-RGNF,New Delhi.Grant No.F.14-2(SC)/2008(SA-Ⅲ)
文摘Objective:To investigate two cyanobacteria isolated from different origins i.e.Lyngbya aestuarii(L.aestuarii)from brackish water and Aphanothece bullosa(4.bullosa)from fresh water paddy fields for antifungal and antileishmanila activity taking Candida albicans and Leishmania donovain as targets.Methods:Biomass of L.aestuarii and A.bullosa were harvested after 40 and60 d respectively and lyophilized twice in methanol(100%)and redissolved in methanol(5%)for bioassay.Antifungal bioassay was done by agar well diffusion method while antileishmanial,by counting cell numbers and flageller motility observation of promastigotes and amastigotes from L.donovani.fluconazole and 5%methanol were used as control.Results:Both the cyanobacteria were found to be potent source of antifungal activity keeping fluconazole as positive control,however,methanolic crude extract(15 mg/mL)of A.bullosa was found more potent(larger inhibition zone)over that of methanolic crude extract of L.aestuarii,Similarly antileishmanial activity of crude extract(24.0 mg/mL)of A.bullosa was superior over that of methanolic crude extract of L.aestuarii(25.6 mg/mL).Conclusions:Antifungal and antileishmanial drugs are still limited in the market.Screening of microbes possessing antifungal and antileishmanial activity drug is of prime importance.Cyanobacteria are little explored in this context because most of the drugs in human therapy are derived from microorganisms,mainly bacterial,fungal and actinomycetes.Thus in the present study two cyanobacterial strains from different origins showed potent source of antifungal and antileishmanial biomolecules.
文摘A series of novel 3-substituted-4-hydroxycoumarin derivatives 6（a-1） were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity（DPPH-radical scavenging activity）. Two compounds, 6h（IC50= 9.90 μmol/L） and 6i（IC50= 6.90 μmol/L） displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine（IC50= 16.15 μmol/L） and miltefosine（IC50= 12.50 μmol/L）. Three compounds, 6c（IC50= 10.79 μmol/L）, 6h（IC50= 10.60 μmol/L）, and 6i（IC50= 10.73 μmol/L） showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene（IC50= 16.47 μmol/L） and ascorbic acid（IC50= 12.69 μmol/L）. A molecular docking study of compounds 6（a-1） suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L.donovani. ADME properties were predicted in silico and support the potential of 6（a-1） to show favorable drug-like properties.
文摘OBJECTIVE:To collect and screen for ethnopharmacological properties(antileishmanial,antibacterial and brine lethality assays) of medicinal plant Ocimum basilicum from Peshawar region(34.008 latitude and 71.57 altitudes).METHODS:In the present study a general antileishmanial activity against Leishmania tropica strain was carried out.The antibacterial potential of the plant was performed against 06 gram positive and 06 gram negative bacteria.Brine shrimp cytotoxicity assay at different concentrations were investigated.RESULTS:The anti-promastigotes profile of the plant showed good antileishmanial activity exhibited LC_(50) value 21.67 μg/mL.The result for gram positive antibacterial activity revealed that the O.basilicum leaves extract possesses significant inhibitory activity at highest two concentrations ranging from20.66 ± 0.31 to 31.86 ± 0.80 for Clostridium perfringens type C and Bacillus subtitilis,respectively,as compared to the gentamycin(27.36 ± 0.55 and21.80 ± 0.72,respectively).For gram negative bacteria good activity was observed.A highest zone of inhibition was recorded for Pseudomonas aeroginosa(28.83 ± 0.28) atthe highest concentration(10 mg/mL).The LC_(50) value obtained for brine shrimp lethality assay was 91.56 μg/mL.CONCLUSION:The herb basil possesses effective cidal activities which make this plant a good candidate for the isolation of antiprotozoal and antibacterial compounds which may lead to the development of novel drug.
文摘Objective:To investigate the biochemical capacity,and in vitro inhibitory effects of hairy roots from two cultivars of Ficus carica L.(Sabz and Siah)on Leishmania major promastigotes and amastigotes.Methods:In the hairy roots,the activity of antioxidant enzymes compared to normal leaves and roots,and the presence of some phenolic compounds in comparison with fruits were investigated.The IC_(50) values of hairy roots in promastigotes was determined by tetrazolium-dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays.By calculating the infectivity index of peripheral blood mononuclear cells(PBMCs),the leishmanicidal activity(IC_(50) values)of hairy roots for amastigotes was estimated.The effects of hairy roots(IC_(50) values)treatment on the levels of IFN-γ and iNOS expression,intracellular reactive oxygen species,and iNOS protein expression in infected-PBMCs were determined.Results:Based on antioxidant enzyme assays and high performance liquid chromatography analysis,hairy roots exhibited high antioxidant capacity and contained high levels of phenolic compounds.According to the results of tetrazolium-dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays,the hairy root extracts of both cultivars showed considerable dose-dependent inhibitory effects against Leishmania major promastigotes.Depending on the concentration and exposure time,treatment of infected-PBMCs with hairy root extracts caused the generation of a significant reactive oxygen species,up-regulation of IFN-γ and iNOS genes expression,and high value of iNOS protein compared to controls.Conclusions:The findings of this study suggest that the hairy roots of Ficus carica can be considered as a promising natural source of antileishmanial agents.
文摘To study the phytochemical constituents and in vitro biological activities of hydromethanolic extract and fractions from Algerian Sahara Myrtus nivellei (M. nivellei) collected in Hoggar region and to identify the active fraction that can act as an alternative of commonly used antibiotics and as antileishmanial or antioxidant agents.MethodsPhytochemical screening of M. nivellei aerial parts was realised according to the literature. Extract was firstly prepared by using aqueous methanol then fractionated with ethyl acetate and butanol solvents. Total phenolics, tannis and flavonoids, of the hydromethanolic extract and their fractions were determined by Folin-Ciocalteu method as gallic acid equivalents and by aluminium chloride as rutin equivalent respectively. Extract and fractions were tested for their antimicrobial and antiparasital activities against standard bacteria using agar diffusion method and two kinds of leishmania visceral and cutaneous. The antioxidant activities were realized using phosphomolybdenum, FRAP and DPPH tests.ResultsPreliminary phytochemical screening exhibited the presence of flavonoids, tannins, saponins, and alkaloids. The experimental results showed that plant extract and fractions were high in phenolic compounds and exhibited an important role as antioxidant, antimicrobial and had a moderate antileishmanial activity.ConclusionsThese observations lead us toward more studies in this field, so that we can get more benefits from our local Algerian medicinal plants.
基金Supported by the Ministry of Education,Addis Ababa,Ethiopia,and DST-Young Scientist Award,SERB(SB/FT/LS-116/2012)New Delhi,and Research Scientist Grant from the University Grants Commission,New Delhi.
文摘Objective:To investigate the seeds of Millettia ferruginea(M.ferruginea)to unravel its antibacterial,antifungal,antitubercular,and antileishmanial potential for the first time.Methods:M.ferruginea seeds were refluxed separately with chloroform,methanol and water to prepare the three extracts,which were tested against the reference strains of Gram-positive and Gram-negative bacteria,yeast cells,Mycobacterium tuberculosis and Leishmania donovani(L.donovani)promastigotes.Next,the seeds were chemically analysed to isolate three constituent compounds,viz.,barbigerone,calopogonium isoflavone-A and durmillone,which were purified,characterised and evaluated for antibacterial and antileishmanial activity.Further,Comet assay was conducted to observe DNA fragmentation effects on human peripheral blood mononuclear cells pretreated with the isoflavonoid compounds.Results:The chloroform and methanol extracts of M.ferruginea seeds exhibited antibacterial and antileishmanial activity.The pure compounds also showed inhibitory activity against Gram-negative ATCC strains(minimum inhibitory concentration~0.5μmol/L),and L.donovani promastigotes(IC_(50)8.2-87.3μg/mL).However,they had little or no activity against yeast cells and tubercle bacilli.The DNA fragmentation study showed that the isoflavonoid constituents of M.ferruginea seeds were safe at therapeutic doses.Conclusions:The antibacterial efficacy of the non-aqueous extracts of M.ferruginea seed was observed against both Gram-positive and Gram-negative ATCC strains.Moreover,the constituents isoflavonoids,viz.,barbigerone,calopogonium isoflavone-A and durmillone,exhibited inhibitory activity against Gram-negative ATCC strains and L.donovani promastigotes.The comet assay showed that the compounds were safe to be considered for human consumption.
文摘The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.
基金This activity was supported by funds from PATH,USA.The funders had no role in the study’s design,data collection and analysis,decision to publish,or preparation of the paper.
文摘Background:Adverse effects of antileishmanial drugs can affect patients’quality of life and adherence to therapy for visceral leishmaniasis(VL)and post-kala-azar dermal leishmaniasis(PKDL).In Bangladesh,there are 26 treatment centers that manage leishmaniasis cases coming from 100 endemic upazilas(subdistricts)of 26 districts(these include VL,PKDL,treatment failure,and relapse VL and cutaneous leishmaniasis cases).This study aimed to investigate the feasibility of using focused pharmacovigilance for VL(VLPV)in Bangladesh’s National Kala-azar Elimination Programme for the early detection and prevention of expected and unexpected adverse drug reactions(ADRs).Methods:This activity has been going on since December 2014.Activity area includes secondary public hospital or Upazila health complex(UHC)in hundred sub districts and Surya Kanta Kala-azar Research Center(SKKRC)in Mymensingh District,a specialized center for management of complicated VL and PKDL cases.Communicable Disease Control(CDC)of the Directorate General of Health Services(DGHS)assigned twenty five of hundred UHCs and SKKRC(total 26)as treatment centers depending on their suitable geographical location.This was implemented for better management of VL cases with Liposomal Amphotericin B(AmBisome®)to ensure patient convenience and proper utilization of this expensive donated drug.A VLPV expert committee and a UHC VLPV team were established,an operational manual and pharmacovigilance report forms were developed,training and refresher training of health personnel took place at UHCs and at the central level,collected information such as patient data including demographics,treatment history and response,adverse events were analyzed.This report includes information for the period from December 2014 to December 2016.Results:From December 2014 to December 2016,1327 leishmaniasis patients were treated and 1066(80%)were available for VLPV.Out of these,57,33,9,and 1%were new VL,PKDL,VL relapse,and other cases,respectively.Liposomal amphotericin B was mostly use
基金supported by Kermanshah University of Medical Sciences(Funding No:97318)。
文摘Objective:Current therapy strategies of leishmaniasis have some problems such as high cost,toxicity and side effects.Plant extracts can be a source of drugs to control leishmaniasis.In this study,the effect of hydroalcoholic and chloroformic extracts of Vigna radiata,Tamarix ramosissima,and Carthamus lanatus on Leishmania major and L.tropica was studied.Methods:The plant samples were collected from west of Iran and their extracts were prepared.Antipromastigote activity assay of all extracts was done using tetrazolium-dye assay.Results:Only high concentrations of V.radiata and C.lanatus were able to inhibit Leishmania,while both high and low concentrations of T.ramosissima had antileishmanial effect.No difference was observed between hydroalcoholic with chloroformic extract of each plant.Conclusion:Altogether,the results revealed the antileishmanial activity of T.ramosissima extracts against L.major and L.tropica,indicating its potential as an antileishmanial agent.
基金Supported by MOES,New Delhi(Grant number SSP003).
文摘Objective:To evaluate the antileishmanial activity of a marine spongeHaliclona oculata.Methods:The crude methanol extract was prepared from the freshly collected sponge and its three fractions were also prepared by maceration method.The antileishmanial activity of these extract and fractions was tested againstLeishmania donovani.Results:The antileishmanial activity was tested bothin vitroand in vivo.The crude methanol extract exerted almost complete inhibition of promastigotes(81.0%±6.9%)and 78.8%±5.2%inhibition of intracellular amastigotes at 100μg/mL with IC_(50)values of 29.5μg/mL and 40.6μg/mL,respectively.The treatment of 500 mg/kg(p.o.)of the crude methanol extract for 5 d for Leishmania donovani infected hamsters resulted in 78.35%±10.20%inhibition of intracellular amastigotes.At a lower dose(250 mg/kg),it exhibited poor efficacy.Among the fractions,highestin vitro(>75%)and in vivo(84.3%±10.2%)antileishmanial activity was observed in n-chloroform fraction with IC_(50)values of 54.2μg/mL and 61μg/mL against promastigotes and intracellular amastigotes,respectively.Hexane fraction andn-butanol(both insoluble and soluble)fractions were found inactivein vitroand in vivo.Conclusions:Our findings indicate that this marine sponge has the potential to provide new insight toward development of an effective antileishmanial agent and,hence,more exhaustive studies are needed for exploiting the vast marine resources of the world to combat the scourge of several parasitic diseases.
