Repurposed organoselenium tethered amidic acids as apoptosis inducers in melanoma cancer <i>via</i> P53, BAX, caspases-3, 6, 8, 9, BCL-2, MMP2, and MMP9 modulations

Abstract

Organoselenium (OSe) agents hold promise for preventing cancer due to their potential ability to fight cancer development and protect cells from oxidative damage. Herein, OSe-based maleanilic and succinanilic acids were tested to estimate their antitumor activities against fifteen cancer cell lines. Besides, their potential safety and selectivity were further investigated against two normal cell lines, namely, human skin fibroblasts (HSF) and olfactory ensheathing cell line (OEC) using the growth inhibition percentage (GI%) assay. Moreover, the apoptotic potential of the superior anticancer candidates (8, 9, 10, and 11) was evaluated against P53, BAX, Caspase-3, Caspase-6, Caspase-8, Caspase-9, BCL-2, MMP2, and MMP9 apoptotic markers. Additionally, to enhance our understanding and predict the inhibitory potential of the examined compounds as potential anticancer agents, a thorough structure-activity relationship (SAR) analysis was conducted. On the other hand, molecular docking and ADMET studies were performed for the examined candidates as well. Overall, our findings point to significant anticancer activities of the organoselenium tethered amidic acids, suggesting their promising cytotoxic potential as effective anticancer drugs.