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

  • ACS Omega. 2025 Feb 10;10(6):5686-5698. doi: 10.1021/acsomega.4c08645.
Ailing Linghu  1  2 ,  Lei Tang  1  2 ,  Qing Li  1  2 ,  Ting Zhong  1  2 ,  Fang Luo  1  2 ,  Xinran Zhao  1  2 ,  Feng Zhang  1  2 ,  Mingzhi Su  1  2 ,  Yanhua Fan  1  2 ,  Linzhen Li  1  2
Affiliations
  • 1. State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China.
  • 2. Natural Products Research Center of Guizhou Province, Guiyang 550014, PR China.
PMID: 39989817 DOI: 10.1021/acsomega.4c08645
Abstract

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.

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