Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs

A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a-x together with thiazoles 13 and 14 were synthesized. Compounds 7a-l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 mu M with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4(+) lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 +/- 0.10 A mu M and 4.8 A +/- 0.08 A mu M against Hep-G2 cell lines, respectively.