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Amide-Linked Monocarbonyl Curcumin Analogues: Efficient Synthesis, Antitubercular Activity and Molecular Docking Study
Polycyclic Aromatic Compounds ( IF 2.4 ) Pub Date : 2020-12-09
Dnyaneshwar D. Subhedar, Mubarak H. Shaikh, Amol A. Nagargoje, Satish V. Akolkar, Sujit G. Bhansali, Dhiman Sarkar, Bapurao B. Shingate

Abstract

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et3NH][HSO4] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC50 values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development.



中文翻译:

酰胺连接的单羰基姜黄素类似物:高效合成,抗结核活性和分子对接研究

摘要

通过芳基醛,哌啶酮和2-氯N-的一锅多组分反应,开发了一种合成具有酰胺键的3,5-双(亚芳基)-4-哌啶酮(DAP)药效团的新型共轭物的方法。苯乙酰胺,使用[Et 3 NH] [HSO 4 ]作为催化剂/介质。亚芳基环和哌啶酮氮(取代的2-氯-N-苯基乙酰胺)上的两个取代都变化。评估了合成的缀合物对结核分枝杆菌H 37 Ra(MTB)和牛分枝杆菌BCG菌株的体外抗结核活性。在系列中,化合物4f4g,4i4j显示出显着的广谱抗结核活性,且IC 50值低。此外,计算机对接模拟中,对于最具活性的缀合物,使用分枝杆菌烯酰基-酰基载体蛋白还原酶(InhA)的活性位点支持抗结核活性。较低的细胞毒性,高效力和对MTBM的有希望的活性。Bovis BCG表明,酰胺连接的DAP可作为进一步修饰和开发的良好线索。

更新日期:2020-12-09
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