TETRAHEDRON
·
2019
·
IF 2.379
Xudong Zheng,Baolong Hou,Rui Wang,Yinyin Wang,Cuiling Wang,Huan Chen,Li Liu,Jilin Wang,Xiumei Ma,Jianli Liu
The natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti -MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human tumor cell lines A549, HCT116 and MDA-MB-231, with mean IC 50 values at low micromolar levels. In addition, some of the compounds showed excellent anti -MRSA activities and were more effective than vancomycin , with MIC values of 0.31–1.25 μg/mL for Mu50,RN4220, and Newman strains.
研究领域:
药理学
·
有机化学
·
微生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Ting Xu,Zihan Xue,Xinhui Li,Miaomiao Zhang,Ruige Yang,Shangshang Qin,Yong Guo
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-acquired infections, necessitating the development of novel antibacterials. Here, we designed and synthesized 30 osthole derivatives with pyridinium quaternary ammonium moieties. In vitro bioassay showed that compounds 8u and 8ac exhibited potent antibacterial activity against S. aureus ATCC 29213 and ten clinical MRSA isolates (MIC = 0.5–1 μg/mL), with low hemolytic activity, rapid bactericidal effects, and minimal resistance induction. In MRSA-infected mouse models of skin abscesses and sepsis, 8u and 8ac also displayed excellent antibacterial effects and safety, which were comparable to vancomycin. Mechanistic studies revealed that 8u and 8ac selectively target bacterial membranes via binding to phosphatidylglycerol (PG), increasing intracellular reactive oxygen species (ROS), inducing content leakage, and ultimately causing bacterial death. These findings suggest 8u and 8ac as promising novel lead candidates for anti-MRSA drug development.
研究领域:
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2015
·Vol. 93
·期 6
·
IF 1.77
Feng Cao,Wei Peng,Xiaoli Li,Ming Liu,Bin Li,Rongxin Qin,Weiwei Jiang,Yanyan Cen,Xichun Pan,Zifei Yan,Kangkang Xiao,Hong Zhou
This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6′-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography – electrospray ionization – tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane.
研究领域:
微生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2024
·Vol. 135
·期 12
·
IF 3.2
Li Jian-Guo,Zhang Chuan-Jian,Liang Liu-Yan,Lu Ting-Yin,Zhong Long-Gen,Zhong Wei-Cheng,Niu Chao-Yan,Sun Jian,Liao Xiao-Ping,Zhou Yu-Feng
AimsMethicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen with multidrug-resistant phenotypes increasingly prevalent in both human and veterinary clinics. This study evaluated the potential of auranofin (AF) as an antibiotic adjuvant to enhance the anti-MRSA activity of florfenicol (FFC) and established a pharmacokinetic/pharmacodynamic (PK/PD) model to compare the efficacy of FFC alone or in combination with AF against MRSA.Methods and resultsWe observed an increased susceptibility and significant synergistic effects of MRSA to FFC in the presence of AF. The combination treatment of FFC and AF significantly inhibited MRSA biofilm formation and decreased the metabolic activity of mature biofilms. Importantly, AF fully restored the efficacy of FFC in both Galleria mellonella larvae and murine models. PK/PD studies demonstrated that the AUC24h/MIC targets required to achieve the bacteriostatic and bactericidal effects were significantly lower with the combination therapy compared to florfenicol monotherapy.ConclusionsThese results reveal the potential of AF as a novel adjuvant to improve the efficacy of FFC in treating MRSA invasive infections and provide valuable PK/PD insights for designing effective combination therapies.
研究领域:
微生物学
·
药理学
·
感染性疾病
✓ 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）