El Diwani Hoda Ibrahim, Abdel-Mohsen Heba Tawfik, Salama Ismail, Ragab Fatma Abdel-Fattah, Ramla Mostafa Mahmoud, Galal Shadia Ahmed, Abdalla Mohamed Mostafa, Abdel-Wahab Abeer, El Demellawy Maha Adel
Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries Research, National Research Center.
Chem Pharm Bull (Tokyo). 2014;62(9):856-66. doi: 10.1248/cpb.c13-01009.
In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90 of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45 µM, respectively) and 6d (IC50/90=0.116/0.452 µM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.
在本研究中，开展了一系列通过亚甲基硫醚键或其生物电子等排体亚甲基氨基桥与取代嘧啶相连的新型苯并咪唑衍生物的合成及对接研究。对所有合成化合物进行了丙型肝炎病毒（HCV）RNA复制抑制活性评估。发现化合物4d、4f和4h比VX - 950更具活性（4d的IC50/90 = 0.123/0.321，4f = 0.145/0.345，4h = 0.129/0.432，VX - 950分别为0.20/0.45 μM），且6d（IC50/90 = 0.116/0.452 μM）显示出与标准品非常相似的活性。化合物4d、4f、4h和6d是有效的HCV RNA复制抑制剂，是进一步研究的良好候选药物。
