Development of trisubstituted thiophene-3-arboxamide selenide derivatives as novel EGFR kinase inhibitors with cytotoxic activity

Abstract

Overexpression of EGFR is one of the eminent oncogenic drivers detected in the development of several human cancers. The increasing incidences of mutation-based resistance in the tyrosine kinase domain call upon the need for the development of a newer class of small-molecule TK inhibitors. Accordingly, a new series of symmetrical trisubstituted thiophene-3-carboxamide selenide derivatives was developed via the hybridization of complementary pharmacophores. Most of the compounds showed a modest to excellent antiproliferative action at 20 μM concentration. The utmost antiproliferative activity was portrayed by compound 16e on the selected cancer cell lines with IC₅₀ < 9 μM, the lowest being 3.20 ± 0.12 μM in the HCT116 cell line. Further, it also displayed an impressive EGFR kinase inhibition with an IC₅₀ value of 94.44 ± 2.22 nM concentration. As a corollary of the reported EGFR inhibition, the nature, energy, and stability of the binding interactions were contemplated via in silico studies.