Design, synthesis and cytotoxic evaluation of novel bis-thiazole derivatives as preferential Pim1 kinase inhibitors with in vivo and in silico study.

Bis-thiazole derivatives were synthesised conforming to the Pim1 pharmacophore model following Hantzsch condensation. Pim1 has a major role in regulating the G1/S phase which upon inhibition the cell cycle stops at its early stages. Derivatives and showed the best Pim1 IC 0.32 and 0.24 µM, respectively relative to staurosporine IC 0.36 µM. Further confirmation of and Pim1 inhibition was implemented by hindering the T47D cell cycle at G0/G1 and S phases where showed 66.5% cells accumulation at G0/G1 phase while demonstrated 26.5% cells accumulation at the S phase compared to 53.9% and 14.9% of a control group for both phases, respectively. Additional cytotoxic evaluation of and revealed strong antitumor activity with up-regulation of caspase-3 and down-regulation of VEGF and TNF immune expression with concomitant elevation of malondialdehyde levels in case of .