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
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
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
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 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
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 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.
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.
