2. Academic Validation
  3. Design, synthesis and anti-tumor evaluation of novel pyrimidine and quinazoline analogues

Design, synthesis and anti-tumor evaluation of novel pyrimidine and quinazoline analogues

  • Eur J Med Chem. 2025 Jan 15:282:117057. doi: 10.1016/j.ejmech.2024.117057.
Ren-Jie Lin 1,  Lin Xie 1,  Tian-Yu Gao 1,  Yi-Zhou Yang 1,  Lan Huang 1,  Kui Cheng 2,  Zhi-Peng Chen 3
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: chengk@smu.edu.cn.
  • 3 Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: czpwyq@smu.edu.cn.
PMID: 39561497 DOI: 10.1016/j.ejmech.2024.117057
Abstract

Disrupting microtubule dynamics has emerged as a promising strategy for Cancer therapy. Novel trimethoxyanilino-substituted pyrimidine and quinazoline derivatives were designed and synthesized to serve as potent microtubule-inhibiting agents with anti-proliferative activity. Compound 2k demonstrates high efficacy against B16-F10 Cancer cells at low nanomolar concentrations, with an IC50 of 0.098 ± 0.006 μM, which is comparable to colchicine. Mechanistic studies have revealed that 2k has the ability to inhibit microtubule protein polymerization in vitro, resulting in cell cycle arrest and Apoptosis. Furthermore, 2k inhibits tumor cell migration and exhibits significant anti-tumor efficacy in a melanoma tumor model without causing obvious toxicity. In summary, the pyrimidine derivative 2k exhibits excellent Anticancer activity and provides a new scaffold for the development of novel microtubule inhibitors, which deserves further in-depth research.

Keywords

Cancer therapy; Pyrimidine; Quinazoline; Tubulin inhibitors.

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