A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a⁻u and N-aryl-pyrazolo[1,5-a]quinazolines 25a⁻c were designed and synthesized via the reaction of 5-aminopyrazoles 11a⁻c with enaminones 12a⁻g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2) and breast (MCF-7) human cancer cells using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2) cells treated with 18o and breast (MCF-7) cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.
Keywords: antitumor activity; cell cycle analysis; pyrazolopyrimidines; pyrazoloquinazolines; synthesis.