Chemical Biology & Drug Design
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2024
·Vol. 103
·期 6
·e14554
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IF 3.2
Hui-xian Liu,Wen-yu Yao,Ge Cui,Jing Zhou,Hao Yan,Hui Guo,Yu-wei Wang,Yue Zhang
This paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2-methyl-4-nitroaniline and 2-methoxy-4-nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by 1 H-NMR, 13 C-NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus , streptococcus , and MRSA strains was determined using the micro broth dilution method. The results showed that the compounds exhibited certain activity against Gram-positive bacteria, among which compounds A8a, A8b, A8c, A8d, and A7 demonstrated superior antibacterial activity against MSSA, MRSA, and pyogeniccoccus compared to tiamulin, although the derivatives showed lower antibacterial activity against streptococcus compared to the control drug. Based on the favorable in vitro activity of A8c, the time-kill kinetics against MRSA were evaluated, revealing that compound A8c could inhibit bacterial proliferation in a concentration-dependent manner.
研究领域:
药理学
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有机化学
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微生物学
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PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 38
·期 7
·1041-1048
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IF 1.828
Huixian Liu,Sui Xiao,Depeng Zhang,Shuhua Mu,Lifang Zhang,Xiaoyang Wang,Feiqun Xue
In this study we describe the design, synthesis, and antibacterial activity of novel pleuromutilin analogs. A series of new compounds containing piperazine and alkylamino or arylamino groups was synthesized. The new compounds were characterized via 1H-NMR, 13C-NMR, Fourier transform (FT)-IR and MS, and were further evaluated for their in vitro activity against seven Gram-positive, and one Gram-negative, pathogens. Antibacterial data revealed that all compounds exhibited moderate to good antibacterial activities against sensitive Gram-positive pathogens. Specifically, 9d displayed the best activity: its activity to Staphylococcus aureus (ATCC25923) is 0.125 µg/mL, which is equal to the control compound tiamulin. The antibacterial activities of 9d to Streptococcus suis (minimum inhibitory concentration (MIC) of 2 µg/mL), Streptococcus agalactiae (MIC of 0.5 µg/mL), and Streptococcus dysgalactiae (MIC of 0.5 µg/mL) were also excellent compared with the control drug erythromycin (MIC of >128 µg/mL). The binding modes of these compounds with active sites were calculated using the programs of Molecular Operating Environment (MOE) and Pymol.
研究领域:
药理学
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有机合成化学
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微生物学
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高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2017
·Vol. 40
·期 8
·1165-1173
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IF 1.683
Shuhua Mu,Huixian Liu,Lifang Zhang,Xiaoyang Wang,Feiqun Xue,Yue Zhang
To develop new pleuromutilin derivatives as veterinary antibiotic medicines, we designed and synthesized a series of new thioether pleuromutilin derivatives possessing acylthiazolyl moiety based on previously designed derivatives. The antibacterial properties of the prepared pleuromutilin derivatives were assessed in vitro by the broth dilution method against five kinds of bacteria and the mycoplasma Mycoplasma gallisepticum (MG). All of the tested compounds displayed moderate to good antibacterial activity to methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-sensitive Staphylococcus epidermidis (MSSE), methicillin-resistant S. aureus (MRSA), Streptococcus agalactiae (S. aga) and MG. However, the activity to Pyogeniccoccus (Pyogens) was generally poor. Compounds 13i and l showed potent antibacterial activity against MSSE and MRSA which are better than that of valnemulin. The structural modification for pleuromutilin affected the antibacterial activity. Amino substituents in the benzene ring can effectively improve activity. Compared with the analogue 13a that possesses unsubstitution benzoyl group, the nitro, methoxy, hydroxy and dichloro substituent contributed little to antibacterial activity. Increasing a methylene between benzene moiety and carbonyl group decreased the bioactivity of derivative. The analogues that obtained by the reaction of amino acids and intermediate 9 showed moderate activity.
研究领域:
药理学
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微生物学
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兽医学
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高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Xirui Xia,Huifang Zhao,Yaxi Li,Xiangyang Long,Xuezhen Liu,Mingyang Bai,Youzhi Tang,Xiangguang Shen,Huanzhong Ding
Mycoplasma gallisepticum ( M. gallisepticum , MG ) is the primary pathogen of chronic respiratory disease ( CRD ) in chickens and leads to pneumonia and air sacculitis in infected chickens and a corresponding economic loss for the poultry industry. The pleuromutilins have excellent anti-mycoplasmal activity and we evaluated the in vivo activity of a new derivative 22-((4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin ( p- furoylamphenmulin ) against M. gallisepticum . A plasma pharmacokinetic ( PK ) study and an in vivo pharmacodynamic ( PD ) study of p -furoylamphenmulin were performed using an M. gallisepticum -infected chicken model. Based on the PK/PD results, a preliminary recommended dose was calculated. The minimum inhibitory concentration ( MIC ) of p -furoylamphenmulin against M. gallisepticum was 0.001953125 μg/mL. PK results indicated that the absorption half-life ( T 1/2ka ) in infected chicks was 0.10 h, elimination half-life ( T 1/2kel ) was 4.23 h. The areas under the concentration-time curve at 24h ( AUC 24h ) for 5, 40, and 80 mg/kg single-dose injections were 1.49, 10.15, and 18.56 μg·h/mL, respectively. The peak concentrations ( C max ) of 5, 40, and 80 mg/kg were 0.56, 5.79, and 9.53 μg/mL, respectively. The PD results indicated that at doses of 70 and 80 mg/kg, the mycoplasmal counts in lungs decreased by 3.39 and 3.28 Log 10 CFU/mL, respectively, achieving a bactericidal effect. Through PK/PD fitting, the target values corresponding to reducing the lung mycoplasma load by 3 Log 10 CFU/mL of AUC 24h /MIC and C max /MIC were 8288.29 h and 4299.30, respectively, and the calculated dosage using formula (2) was 62.64 mg/kg, under the regimen of intramuscular injection once every 24 h for 3 consecutive days. In addition, the effect of high-dose p -furoylamphenmulin on the relief of air sac lesions was significant. These results provide a basis for developing and applying p -furoylamphenmulin and provide a preliminary medication regimen.
研究领域:
兽医学
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药理学
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感染病学
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PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 12
·e82595
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IF 3.73
Ruofeng Shang,Shengyu Wang,Ximing Xu,Yunpeng Yi,Wenzhu Guo,YuLiu,Jianping Liang
Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA.
研究领域:
药物化学
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微生物学
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DOI
PubMed
高影响因子
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