Efficient synthesis and cell migration inhibitory effect of substituted benzamidothiazolylpyrazole-capped AWD*I-NH2

Article abstract of DOI:10.1016/j.bmcl.2019.126914

Substituted (2-benzamidothiazol-5-yl)pyrazole-capped AWD*I-NH₂ were synthesized and their antimigration activity was studied. The improved efficiency and scalability of the analog synthesis was achieved via a late-stage diversification of the benzoyl group and a convergent route in which the bisazole capping agents and off-resin peptide AWD*I-NH₂ were prepared in parallel and coupled together in solution at the last step. Bioassay results indicate that all the peptidomimetics can significantly inhibit the migration of breast cancer cells MDA-MB-231 but possess no apparent cytotoxicity. In general, the antimigration potency of the peptidomimetics is correlated to the electron-withdrawing capacity of the substituents on the terminal phenyl ring. The inhibitory effect shows dose-dependent and holds also against lung and cervical cancer cells. The level of f-actin was reduced dramatically in cells treated with the inhibitor, suggesting that the migration inhibitory effect is related to the disruption of cell locomotive protrusions.