Synthesis and Antitumor Activity of 6-(2-Aminobenzo[d]thiazol-5-yl) quinazolin-4(3H)-one Derivatives.

Quinazolinones are key scaffolds in anticancer drug development. We previously identified the lead compound 16h from a series of 6-(1H-benzo[d]imidazol-6-yl) quinazolin-4(3H)-one derivatives. In this study, we optimized 16h to develop new 6-(2-aminobenzo[d]thiazol-5-yl) quinazolin-4(3H)-one derivatives, with compound 45 showing the best antiproliferative activity against A549 lung cancer cells (IC50: 0.44 μM) and good selectivity. Mechanistic studies revealed that compound 45 induced G1-phase arrest, inhibited ALK/PI3K/AKT signaling, disrupted mitochondrial membrane potential, and promoted apoptosis. It also significantly inhibited spheroid formation in a 3D cell culture model. In summary, the results suggest that compound 45 might have potential for the development of anticancer drugs.