Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 6
·e14554
·
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
·
有机化学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbial Drug Resistance
·
2020
·Vol. 26
·期 2
·100-109
·
IF 2.519
Chong-Fa Lai,Wei-Bin Xiao,Hua-Cheng Yan,Hui Yang,Lu-Xia Wang,Hui Guan,Qiu-ju Peng,Zhi-Rong Deng,Jian-Wen Chen,Lin-Kun An,Lei Shi
ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). In our study, the MIC90s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA, n = 200), methicillin-sensitive S. aureus (MSSA, n = 100), Enterococcus faecalis (E. faecalis, n = 32), and Enterococcus faecium (E. faecium n = 32) were 0.25, 0.25, 0.125, and 8 μg/mL, respectively, whereas the MBC90s (minimum bactericidal concentrations) were 2, 1, 1, and >32 μg/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5–9) and in starting inoculum size up to 107 CFU/mL. The presence of human serum (25–75%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and E. faecalis strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4 × and 8 × ). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses <50 mg/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI = IC50/MIC90) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and E. faecalis strains. Moreover, the in vivo efficacy (effective dose [ED]50 = 6.59 mg/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.
研究领域:
微生物学
·
药理学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）