- 作者: 侯曼貞,楊家欣,連金城,郭盛助,黃麗嬌
- 作者服務機構: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
- 中文摘要: In our continuing search for potential anticancer candidates, 2-(3-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (JJC-1) was selected as the lead compound. Starting 5-pyrrolidinyl-2-aminobenzamide was prepared using standard methodology from 5-chloro-2-nitrobenzoic acid by reaction with SOCl2, NH3, pyrrolidine, and H2. The starting benzamide then was reacted with 2-substituted benzaldehyde or benzoyl chloride in N,N-dimethylacetamide (DMAC) in the presence of NaHSO3 at 150 °C. Thermal cyclodehydration/dehydrogenation gave the target 6-pyrrolidinyl-2-(2-substituted phenyl)-4-quinazolinones (15-22). These target compounds were assayed for their cytotoxicity in vitro against six cancer cell lines, including human monocytic leukemia cells (U937), mouse monocytic leukemia cells (WEHI-3), human hepatoma cells (HepG2, Hep3B) and human lung carcinoma cells (A549,H27). Most of them exhibited significant cytotoxic effect toward U937 and WEHI-3 cells, with EC50 values ranging from 0.30 to 10.10 mM. Compound 19 was investigated further for its action mechanisms. Preliminary findings indicated that compound 19 induced G2/M arrest and apoptosis on U937 cells.
- 英文摘要: --
- 中文關鍵字: Cytotoxicity; 6-Pyrrolidinyl-2-(2-substituted phenyl)-4-quinazolinones; Leukemia cells.
- 英文關鍵字: --