Design, synthesis and biological evaluation of 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles as inhibitors of ebola virus infection

Novel 2-substituted-6-[(4-substituted-1-piperidyl)methyl]-1H-benzimidazoles were designed and synthesized as Ebola virus inhibitors. The proposed structures of the new prepared benzimidazole-piperidine hybrids confirmed based on their spectral data CHN analyses. target compounds screened in vitro for anti-Ebola activity. Among tested molecules, 26a (EC50=0.93 ?M, SI = 10) 25a (EC50=0.64 20) potent more selective than Toremifene reference drug (EC50 0.38 7) against cell line. Data suggests that mechanism by which block EBOV infection is through inhibition viral entry at level NPC1. Furthermore, a docking study revealed several NPC1 amino acids participate binding to GP are involved most active 26a. Finally, silico ADME prediction indicates an idealy drug-like candidate. Our results could enable development small molecule capable inhibiting virus, especially step.