抗细菌
药效团
吡啶
异烟肼
结核分枝杆菌
生物信息学
化学
部分
对接(动物)
体内
组合化学
立体化学
体外
利福平
药理学
肺结核
生物化学
抗生素
生物
有机化学
医学
护理部
生物技术
病理
基因
作者
Gollagani Vijaya Bhavani,Sree Karani Kondapuram,Aifa Fathima Shamsudeen,Mohane Selvaraj Coumar,Joseph Selvin,Tharanikkarasu Kannan
摘要
Abstract In the quest to develop potent inhibitors for Mycobacterium tuberculosis , novel isoniazid‐based pyridinium salts were designed, synthesized, and tested for their antimycobacterial activities against the H 37 Rv strain of Mycobacterium tuberculosis using rifampicin as a standard. The pyridinium salts 4k, 4l , and 7d showed exceptional antimycobacterial activities with MIC 90 at 1 µg/mL. The in vitro cytotoxicity and pharmacokinetics profiles of these compounds were established for the identification of a lead molecule using in vivo efficacy proof‐of‐concept studies and found that the lead compound 4k possesses LC 50 value at 25 µg/mL. The in vitro antimycobacterial activity results were further supported by in silico studies with good binding affinities ranging from −9.8 to −11.6 kcal/mol for 4k, 4l , and 7d with the target oxidoreductase DprE1 enzyme. These results demonstrate that pyridinium salts derived from isoniazid can be a potentially promising pharmacophore for the development of novel antitubercular candidates.
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