In order to probe the effect of C-2(S)-substituted groups in the antibacterial activity,a series of novel C-2(S)-substituted pleuromutilin analogues of SB-225586 were synthesized and evaluated for their in vitro antib...In order to probe the effect of C-2(S)-substituted groups in the antibacterial activity,a series of novel C-2(S)-substituted pleuromutilin analogues of SB-225586 were synthesized and evaluated for their in vitro antibacterial activity.The results of antibacterial activities indicated that C-2(S)-substituted pleuromutilin derivatives retained appreciable antibacterial activity,and the 2-fluorination compounds 6a and 6b are more potent than the corresponding 2-hydroxylation analogues 7a and 7b.展开更多
In order to find novel antibacterial agents with superior antibacterial activity and overcoming multidrug resistance,a series of pleuromutilin derivatives with novel C（14） side chain were synthesized and evaluated f...In order to find novel antibacterial agents with superior antibacterial activity and overcoming multidrug resistance,a series of pleuromutilin derivatives with novel C（14） side chain were synthesized and evaluated for their in vitro antibacterial activities.The results of antibacterial acticities indicated that most of the derivatives showed potent activities against Gram-positive organisms.In particular,compound lOd exhibited the most potent inhibitory activity compared with pleuromutilin and linezoid,emerged as potential molecule for further investigation.展开更多
Six new pleuromutilin derivatives were designed and synthesized, confirmed by MS, IR and ^1H NMR techniques. And the antibacterial activities were primarily evaluated in vitro. The results indicated that most of the d...Six new pleuromutilin derivatives were designed and synthesized, confirmed by MS, IR and ^1H NMR techniques. And the antibacterial activities were primarily evaluated in vitro. The results indicated that most of the derivatives showed more potent activities against corresponding bacterial strains than that of pleuromutilin. Especially, compounds 4d and 5b had obvious activities against salmonella compared with pleuromutilin.展开更多
Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus alo...Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified.105 Enterococcus isolates were obtained from 115 environmental samples (air,dust,feces,fies,sewage,and soil) collected along the laying hen production chain (breeding chicken,chick,young chicken,and commercial laying hen).These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics,such as tetracycline (92.4%),streptomycin (92.4%),and erythromycin (91.4%),and all strains had multidrug resistance phenotypes.Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51pleuromutilin-resistant Enterococcus isolates,and lsa(E),which mediates resistance to pleuromutilins,always co-occurred with lnu(B).Alignments with the Mobile Genetic Elements database identified four transposons (Tn554,Tn558,Tn6261,and Tn6674) with several ARGs(erm(A),ant(9)-la,fex(A),and optrA) that mediated resistance to many clinically important antibiotics.Moreover,we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492.A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms.Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention,and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain,thereby warranting effective disinfection.展开更多
A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of ...A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12 a, 12 d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.展开更多
Two new pleuromutilin derivatives, 14-O-[（4-amino-6-methoxyl-pyrimidine-2-yl）-thioacetyl] mutilin（4） and 14-O-[4-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl）thioacetyl] mutilin（5）, were synthesized and struc...Two new pleuromutilin derivatives, 14-O-[（4-amino-6-methoxyl-pyrimidine-2-yl）-thioacetyl] mutilin（4） and 14-O-[4-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl）thioacetyl] mutilin（5）, were synthesized and structurally characterized by IR, NMR spectra, HRMS and single-crystal X-ray diffraction. These compounds contain a 5-6-8 tricyclic carbon skeleton and a pyrimidine ring. Compound 4 is in the monoclinic system, space group P1211 with a = 10.2517（4）, b = 12.5655（4）, c = 10.3435（4）A, V = 1315.69（8） A^3, Z = 2, Dc = 1.309 g/cm3, F（000） = 558, μ = 0.166 mm^-1, S = 1.047, R = 0.0457 and w R = 0.0934 for 4721 unique reflections（R（int） = 0.0322） with I 〉 2σ（I）. Compound 5 belongs to the orthorhombic system, space group P212121 with a = 7.3667（4）, b = 13.9990（7）, c = 29.0434（13） A, V = 2995.1（2） A^3, Z = 4, Dc = 1.250 g/cm^3, F（000） = 1216, μ = 0.153 mm^-1, S = 1.031, R = 0.0545 and wR = 0.0982 for 5242 unique reflections（R（int） = 0.0476） with I 〉 2σ（I））. The in vitro antibacterial activity study showed the title compounds 4 and 5 displayed slightly less activity against methicillin-resistant Staphylococcus aureus（MRSA） and methicillin-resistant Staphylococcus epidermidis（MRSE）, and lower potent against Escherichia coli（E.coli） and Bacillus subtilis（B.subtilis） when compared to those of tiamulin fumarate.展开更多
A new pleuromutilin derivative, 14-O-[（4,6-diaminopyrimidine-2-yl） thioacetate] mutilin, was synthesized and structurally characterized by IR, NMR spectra and single-crystal X-ray diffraction. This compound contains...A new pleuromutilin derivative, 14-O-[（4,6-diaminopyrimidine-2-yl） thioacetate] mutilin, was synthesized and structurally characterized by IR, NMR spectra and single-crystal X-ray diffraction. This compound contains a 5-6-8 tricyclic carbon skeleton and a pyrimidine ring. Its crystal is of orthorhombic system, space group P21 with a = 10.0237（6）, b = 12.6087（7）, c = 10.3749（8） A, fl = 101.48（1）°, V = 1284.99（14） A3, Z = 2, F（000） = 540, Oc（Mg/m3） = 1.299, # = 0.165 mm1, R = 0.0649 and wR = 0.0797. The in vitro antibacterial activity study using Oxford cup assay showed this compound displayed more potent activity than pleuromutilin and similar antibacterial activity to that oftiamulin.展开更多
文摘In order to probe the effect of C-2(S)-substituted groups in the antibacterial activity,a series of novel C-2(S)-substituted pleuromutilin analogues of SB-225586 were synthesized and evaluated for their in vitro antibacterial activity.The results of antibacterial activities indicated that C-2(S)-substituted pleuromutilin derivatives retained appreciable antibacterial activity,and the 2-fluorination compounds 6a and 6b are more potent than the corresponding 2-hydroxylation analogues 7a and 7b.
基金National Science and Technology Major Project for the support of this researchsupported by Key New Drug Creation and Manufacturing Program,China(No:2009ZX09301-001)
文摘In order to find novel antibacterial agents with superior antibacterial activity and overcoming multidrug resistance,a series of pleuromutilin derivatives with novel C（14） side chain were synthesized and evaluated for their in vitro antibacterial activities.The results of antibacterial acticities indicated that most of the derivatives showed potent activities against Gram-positive organisms.In particular,compound lOd exhibited the most potent inhibitory activity compared with pleuromutilin and linezoid,emerged as potential molecule for further investigation.
文摘Six new pleuromutilin derivatives were designed and synthesized, confirmed by MS, IR and ^1H NMR techniques. And the antibacterial activities were primarily evaluated in vitro. The results indicated that most of the derivatives showed more potent activities against corresponding bacterial strains than that of pleuromutilin. Especially, compounds 4d and 5b had obvious activities against salmonella compared with pleuromutilin.
基金supported by the National Key Research and Development Program of China (Nos.2022YFC2303900 and2022YFD1800400)the General Program of National Natural Science Foundation of China (Nos.U21A20257 and 31830098)+1 种基金the National System of Layer Production Technology (No.CARS-40-K-14)the Key R&D Program of Sichuan Province (Nos.2022ZDZX0017 and 2021YFH0192)。
文摘Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified.105 Enterococcus isolates were obtained from 115 environmental samples (air,dust,feces,fies,sewage,and soil) collected along the laying hen production chain (breeding chicken,chick,young chicken,and commercial laying hen).These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics,such as tetracycline (92.4%),streptomycin (92.4%),and erythromycin (91.4%),and all strains had multidrug resistance phenotypes.Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51pleuromutilin-resistant Enterococcus isolates,and lsa(E),which mediates resistance to pleuromutilins,always co-occurred with lnu(B).Alignments with the Mobile Genetic Elements database identified four transposons (Tn554,Tn558,Tn6261,and Tn6674) with several ARGs(erm(A),ant(9)-la,fex(A),and optrA) that mediated resistance to many clinically important antibiotics.Moreover,we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492.A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms.Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention,and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain,thereby warranting effective disinfection.
文摘A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12 a, 12 d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.
基金Basic Scientific Research Funds in Central Agricultural Scientific Research Institutions(No.1610322014003)the Agricultural Science and Technology Innovation Program(ASTIP,No.CAAS-ASTIP-2014-LIHPS-04)
文摘Two new pleuromutilin derivatives, 14-O-[（4-amino-6-methoxyl-pyrimidine-2-yl）-thioacetyl] mutilin（4） and 14-O-[4-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl）thioacetyl] mutilin（5）, were synthesized and structurally characterized by IR, NMR spectra, HRMS and single-crystal X-ray diffraction. These compounds contain a 5-6-8 tricyclic carbon skeleton and a pyrimidine ring. Compound 4 is in the monoclinic system, space group P1211 with a = 10.2517（4）, b = 12.5655（4）, c = 10.3435（4）A, V = 1315.69（8） A^3, Z = 2, Dc = 1.309 g/cm3, F（000） = 558, μ = 0.166 mm^-1, S = 1.047, R = 0.0457 and w R = 0.0934 for 4721 unique reflections（R（int） = 0.0322） with I 〉 2σ（I）. Compound 5 belongs to the orthorhombic system, space group P212121 with a = 7.3667（4）, b = 13.9990（7）, c = 29.0434（13） A, V = 2995.1（2） A^3, Z = 4, Dc = 1.250 g/cm^3, F（000） = 1216, μ = 0.153 mm^-1, S = 1.031, R = 0.0545 and wR = 0.0982 for 5242 unique reflections（R（int） = 0.0476） with I 〉 2σ（I））. The in vitro antibacterial activity study showed the title compounds 4 and 5 displayed slightly less activity against methicillin-resistant Staphylococcus aureus（MRSA） and methicillin-resistant Staphylococcus epidermidis（MRSE）, and lower potent against Escherichia coli（E.coli） and Bacillus subtilis（B.subtilis） when compared to those of tiamulin fumarate.
基金Supported by Basic Scientific Research Funds in Central Agricultural Scientific Research Institutions(No.1610322014003)the Agricultural Science and Technology Innovation Program(ASTIP)
文摘A new pleuromutilin derivative, 14-O-[（4,6-diaminopyrimidine-2-yl） thioacetate] mutilin, was synthesized and structurally characterized by IR, NMR spectra and single-crystal X-ray diffraction. This compound contains a 5-6-8 tricyclic carbon skeleton and a pyrimidine ring. Its crystal is of orthorhombic system, space group P21 with a = 10.0237（6）, b = 12.6087（7）, c = 10.3749（8） A, fl = 101.48（1）°, V = 1284.99（14） A3, Z = 2, F（000） = 540, Oc（Mg/m3） = 1.299, # = 0.165 mm1, R = 0.0649 and wR = 0.0797. The in vitro antibacterial activity study using Oxford cup assay showed this compound displayed more potent activity than pleuromutilin and similar antibacterial activity to that oftiamulin.
