In the pursuit of novel therapeutic agents: synthesis, anticancer evaluation, and physicochemical insights of novel pyrimidine-based 2-aminobenzothiazole derivatives

Abstract

Cancer remains a worldwide healthcare undertaking, demanding continual innovation in anticancer drug development due to frequent drug resistance and adverse effects associated with existing therapies. The benzothiazole compounds, particularly 2-aminobenzothiazole derivatives, have attracted interest for their versatility in generating novel anticancer agents. This study explores the synthesis, and anticancer evaluation of new pyrimidine-based 2-aminobenzothiazole derivatives. A range of synthetic methods have been developed based on the reaction of 2-benzothaizolyl guanidine with various reagents such as α,β-unsaturated carbonyl, 2-cyano-three-(dimethylamino)-<i>N</i>-acrylamide, β-diketones, β-keto esters, and <i>S</i>,<i>S</i> ketene dithioacetals. Human tumour cell lines such as HepG2, HCT116, and MCF7 were used in <i>in vitro</i> cytotoxicity studies, and the results showed that several of the synthesized compounds were more potent than the standard drug, 5-fluorouracil, in terms of cell viability% with low IC₅₀. Furthermore, the computed drug likeness and ADMET properties of the most potent synthesized compounds suggest their potential as promising candidates for further development, with favorable bioavailability and pharmacokinetic profiles.