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

摘要

A series of oxadiazole (>7a-l) and hydroxypyrazoline derivatives (>8a-l) incorporating thiazole were synthesized and characterized by spectral analysis (¹H-NMR, ¹³C-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.