Synthesis and Antitumor Activity of 6-(2-Aminobenzo[<i>d</i>]thiazol-5-yl) quinazolin-4(3<i>H</i>)-one Derivatives
Quinazolinones are key scaffolds in anticancer drug development. We previously identified the lead compound <b>16h</b> from a series of 6-(1<i>H</i>-benzo[<i>d</i>]imidazol-6-yl) quinazolin-4(3<i>H</i>)-one derivatives. In this study, we optimized <b>16h</b> to develop new 6-(2-aminobenzo[<i>d</i>]thiazol-5-yl) quinazolin-4(3<i>H</i>)-one derivatives, with compound <b>45</b> showing the best antiproliferative activity against A549 lung cancer cells (IC<sub>50</sub>: 0.44 μM) and good selectivity. Mechanistic studies revealed that compound <b>45</b> 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 <b>45</b> might have potential for the development of anticancer drugs.
Authors
- Xinran Zhao (ORCID: https://orcid.org/0000-0003-0107-6077)
- Linzhen Li (ORCID: https://orcid.org/0000-0003-2406-9160)
- Yanhua Fan (ORCID: https://orcid.org/0000-0002-8973-2384)
- Ting Zhong (ORCID: https://orcid.org/0000-0001-7545-8268)
- Ailing Linghu
- Feng Zhang (ORCID: https://orcid.org/0000-0003-2887-8184)
- Fang Luo
- Lei Tang
- Mingzhi Su
- Qing Li (ORCID: https://orcid.org/0000-0001-7395-4313)
Institutions
- Guiyang Medical University (CN)
- Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences (CN)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-02-10
- DOI
- https://doi.org/10.1021/acsomega.4c08645
- Primary Topic
- Quinazolinone synthesis and applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Guizhou Medical University
- Science and Technology Program of Guizhou Province