JOURNAL OF ANTIBIOTICS
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2021
·Vol. 74
·期 9
·574-579
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IF 2.649
Ge Ying,Kang Peng-Wei,Li Jia-Qi,Gao Han,Zhai Le,Sun Le-Yun,Chen Cheng,Yang Ke-Wu
The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones ( 1a - 1m ) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC 50 in the range of 0.88–20.2 µM, and 1a and 1f were found to be the potent inhibitors (IC 50 = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml −1 ) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.
研究领域:
微生物学
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药理学
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感染病学
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DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2024
·
IF 4.4
Peifang Wang,Yue Su,Min Ma,Yuqing Wang,Shuang Hou,Changqing Wang,Lin Sun,Jianshe Wei,Mingxue Li
An injectable hydrogel loading α-N-heterocyclic thiosemicarbazones with antibacterial activity was designed to attain therapy against wounds with high efficiency. In the present study, the injectable FPZ-H2L hydrogel was synthesized by loading 2,6-diacetylpyridine bis(N4-methylthiosemicarbazone) (H2L) on transition-metal ions (Zn2+)-cross-linked-folic acid (FA)-co-polydopamine (PDA) hydrogel (FPZ hydrogel). The injectable hydrogel (FPZ-H2L) cross-linked by coordination and hydrogen bonds displayed an excellent self-healing performance and completely covered the irregular wound. Compared with the FPZ hydrogel, the FPZ-H2L hydrogel has stronger antibacterial efficacy on typical Gram-positive/negative bacteria and drug-resistant bacteria. The antibacterial mechanisms of the hydrogel were related to biofilm ablation, the disruption of the cell membrane integrity, leakage of nucleic acids and proteins, and the production of oxidative stress response, thus causing bacterial death. Cell Counting Kit-8 (CCK-8) test shows that FPZ-H2L hydrogel has excellent cell compatibility, and gel drug loading technology greatly overcomes the problem of high cytotoxicity of H2L. The wound healing experiments indicated that the hydrogel enhanced the wound healing efficacy of mice. These results prove that the mixed hydrogel has broadened the field of vision for the design of antibacterial wound dressings.
研究领域:
生物材料学
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医学
·
药剂学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2015
·
IF 3.447
Xu-Meng Zhang,Hui Guo,Zai-Shun Li,Fu-Hang Song,Wei-Min Wang,Huan-Qin Dai,Li-Xin Zhang,Jian-Guo Wang
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have caused an increasing mortality rate, which means that antibiotic resistance is becoming an important health issue. In the course to screen new agents for resistant bacteria, we identified that a series of isatin-β-thiosemicarbazones (IBTs) could inhibit the growth of MRSA and VRE. This was the first time that the “familiar” IBT compounds exhibited significant anti Gram-positive pathogen activity. Against a clinical isolated MRSA strain, 20 of the 51 synthesized compounds showed minimum inhibitory concentration (MIC) data of 0.78 mg/L and another 12 novel compounds had MICs of 0.39 mg/L. Moreover, these compounds also inhibited Enterococcus faecalis and VRE at similar levels, indicating that IBTs might have different mode of action compared with vancomycin . For these IBTs, comparative field analysis (CoMFA) models were further established to understand the structure–activity relationships in order to design new compounds from steric and electrostatic contributions. This work has suggested that IBTs can be considered as potential lead compounds to discover antibacterial inhibitors to combat drug resistance.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jiangli Song,Hanlian Chen,Rongkai Pan,Fangyu Jin,Jie Tang,Qianqian Huang,Guohua Zhou,Xiumei Song
Understanding the interactions between small molecules and calf thymus deoxyribonucleic acid (ctDNA) is critical for certain aspects of drug discovery. In this study, three 11 H -indeno[1,2-b]quinoxalin-11-one thiosemicarbazones were synthesized and their interaction with ctDNA was examined through various spectroscopic techniques, including ultraviolet (UV) spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectrum, and through physicochemical methods, including viscosity measurements. In addition, the effects of these thiosemicarbazone compounds 4a, 4b and 4c on several cancer cell lines were explored. The results of UV absorption, fluorescence quenching and CD experiments indicated that compounds 4a, 4b and 4c primarily bound to ctDNA by an intercalation. This mode of interaction was further corroborated by viscosity measurements. Docked poses of compound 4a revealed that it formed a crucial N position hydrogen bond with the DNA receptor. The chemical structure of compound 4a was further confirmed by X-ray crystallographic analysis. Through biological evaluation, it was found that the in vitro cytotoxicity of three compounds agreed with the order of their binding strength to ctDNA, indicating that the antitumor activity of these compounds correlated with their binding affinity to ctDNA.
研究领域:
生物化学
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药物化学
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肿瘤学
✓ 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）