Design, synthesis, and pharmacology of some oxadiazole and hydroxypyrazoline hybrids bearing thiazoyl scaffold: antiproliferative activity, molecular docking and DNA binding studies.

A series of oxadiazole (7a-l) and hydroxypyrazoline derivatives (8a-l) incorporating thiazole were synthesized and characterized by spectral analysis ((1)H-NMR, (13)C-NMR, Mass, and FT-IR). The synthesized compounds were screened for their in vitro cytotoxicity against MDA-MB231 and HT-29 human cell lines. Conjugates 7d, 7e, 7f, 7i, 7l, 8a, 8b, 8i and 8l exhibited significant antiproliferative activity on both MDA-MB231 and HT-29 cell lines. Flow cytometric analysis reveals that, 7i arrests both cells lines at Go/G1 phase whereas 8i induced G0/G1 arrest only in the HT-29 cells. Furthermore, Computational interaction studies of 7i and 8i exhibited its capacity of being a plausible CDK2 and BCL-2 inhibitor respectively. In addition, DNA binding of the synthesized compounds and DNA docking of 7i and 8i demonstrated the ability to interact with DNA. Compounds 7i and 8i causes' remarkable growth inhibition of MDA-MB231 and HT-29 cells but compound 8i was considerably effective against HT-29 cells. Overall these compounds can be practiced for further drug development.