M. Hour, Jai-Sing Yang, J. Lien
Jun 1, 2007
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0
Influential Citations
14
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Journal
Journal of The Chinese Chemical Society
Abstract
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, CH27). Most of them exhibited significant cytotoxic effect toward U937 and WEHI-3 cells, with EC50 values ranging from 0.30 to 10.10 μM. Compound 19 was investigated further for its action mechanisms. Preliminary findings indicated that compound 19 induced G2/M arrest and apoptosis on U937 cells.