Design, Synthesis, and Biological Evaluation of 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole Derivatives as Anti-HIV-1 Agents.

A novel series of 1-(thiophen-2-yl)-9H-pyrido [3,4-b]indole derivatives were synthesized using DL-tryptophan as starting material. All the compounds were characterized by spectral analysis such as (1) H NMR, Mass, IR, elemental analysis and evaluated for inhibitory potency against HIV-1 replication. Among the reported analogues, compound 7g exhibited significant anti-HIV activity with EC(50) 0.53 μm and selectivity index 483; compounds 7e, 7i, and 7o displayed moderate activity with EC(50) 3.8, 3.8, and 2.8 μm and selectivity index >105, >105, and 3.85, respectively. Interestingly, compound 7g inhibited p24 antigen expression in acute HIV-1(IIIB) infected cell line C8166 with EC50 1.1 μm. In this study, we also reported the Lipinski rule of 5 parameters, predicted toxicity profile, drug-likeness, and drug score of the synthesized analogues.