Sheshagiri R Dixit, Shrinivas D Joshi, Venkatarao H Kulkarni, Sunil S Jalalpure, Vijay M Kumbar, Tulasigiriyappa Y Mudaraddi, Mallikarjuna N Nadagouda, Tejraj M Aminabhavi
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引用次数: 5
摘要
简介:为了开发新的抗结核化合物，本文描述了15种新合成的吡咯酰吡唑啉甲酸酯的细胞毒性评价。方法与材料:采用曲面对接法研究结核分枝杆菌(Mycobacterium tuberculosis, M. tuberculosis)酶烯丙基ACP还原酶活性位点化合物的结合模式，该酶在结核分枝杆菌FAS-II生物合成途径中起重要作用，也是设计新型抗结核药物的重要靶点。结果:在合成的化合物中，化合物4g和4i与MET98、TYR158和辅因子NAD+均表现出h键相互作用，均与InhA的结合口袋内吻合良好。此外，这些化合物显示出与4TZK配体相同的相互作用类型。进一步评价了化合物对结核分枝杆菌H37Rv株的初步抗结核活性。结论:利用人肺癌细胞系(A549)对某些化合物进行了哺乳动物细胞毒性筛选，发现它们是无毒的。
Pyrrolyl Pyrazoline Carbaldehydes as Enoyl-ACP Reductase Inhibitors: Design, Synthesis and Antitubercular Activity.
Introduction: In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.
Method & materials: Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from Mycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway of M. tuberculosis and also it is an important target for designing novel anti-TB agents.
Results: Among the synthesized compounds, compounds 4g and 4i showed H-bonding interactions with MET98, TYR158 and co-factor NAD+, all of which fitted well within the binding pocket of InhA. Also, these compounds have shown the same type of interaction as that of 4TZK ligand. The compounds were further evaluated for preliminary anti-TB activities against M. tuberculosis H37Rv strain.
Conclusion: Some compounds were also screened for their mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic.
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