Synthesis, anti-HIV-1 and antiproliferative evaluation of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety

In an effort to synthesize more effective non-nucleoside reverse transcriptase inhibitors (NNRTIs) against the HIV-1 infection, a new series of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety were designed by molecular docking studies, prepared and characterized by spectroscopic techniques. All the synthesized compounds were in vitro evaluated for their inhibitory effect against the HIV-1 replication in the MT-4 cells. Results showed that none of these synthesized compounds displayed any specific anti HIV-1 activity. Surprisingly, these compounds showed high cytotoxicity against MT-4 cells with low selectivity index (<1), therefore could be new potential antiproliferative agents. Therefore, their antiproliferative property were evaluated against MOLM-13 and K562 (leukemia) cell lines. Compound 14g showed notable antitumor activity toward both studied cell lines (EC50 = 1.3 mu M and EC50 = 1.8 mu M respectively). (C) 2019 Elsevier B.V. All rights reserved.