Negi Beena, Poonan Prija, Ansari Mohammad Fawad, Kumar Deepak, Aggarwal Sakshi, Singh Ramandeep, Azam Amir, Rawat Diwan S
Department of Chemistry, University of Delhi, Delhi, 110007, India.
Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, India.
Eur J Med Chem. 2018 Apr 25;150:633-641. doi: 10.1016/j.ejmech.2018.03.033. Epub 2018 Mar 13.
A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC = 0.12-0.35 μM) than the reference drug metronidazole (IC = 1.79 μM). The most active compounds were found to be non-toxic (up to 50 μM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein.
合成了一系列22种新型甲硝唑-三唑-苯乙烯基杂化物，并对其针对溶组织内阿米巴HM1:IMSS菌株的体外抗阿米巴活性进行了评估。发现一些杂化物比参比药物甲硝唑（IC = 1.79 μM）更具活性（IC = 0.12 - 0.35 μM）。发现活性最高的化合物对Vero细胞无毒（高达50 μM），表明这些杂化物具有良好的安全性。还进行了对接和ADMET研究以探究可能的作用模式。对接研究显示在溶组织内阿米巴硫氧还蛋白还原酶（EhTrR）蛋白的活性位点有显著的结合亲和力。
