Design, synthesis and cytotoxic research of a novel antitumor model based on acrylamide–PABA analogs via β-tubulin inhibition

Abstract

Currently, the human health is facing numerous challenges, especially with regard to cancer. Therefore, new treatment options that specifically target tumor cells will inevitably improve the therapeutic toolkit for various cancers. In this regard, a sequence of acrylamide–PABA hybrids 4a–j was synthesized, and their formation was confirmed via spectral and elemental analyses. The compounds were evaluated for their antiproliferative activity against MCF-7 (breast), HepG2 (liver) and a normal health breast cell line (MCF-10A). Among the series, acrylamide–PABA analog 4j with a furan group in the acrylamide moiety was the most potent anti-proliferative member with a notable IC₅₀ value (IC₅₀ = 1.83 μM) against MCF-7 cells. Compound 4j's anti-tubulin activity and apoptosis-promoting properties were the cause of its anti-proliferative inhibitory mechanism. Compound 4j promoted apoptosis in MCF-7 cells by raising the expression of apoptotic markers, such as p53, Bax, Bcl-2 and caspase 9, with respect to the untreated control. The molecular docking study of compound 4j revealed a nice fitting into the active site of tubulin.