Abstract
The reaction of cyclohexan-1,3-dione with either of malononitrile or ethyl cyanoacetate gave the 4-amino-6,7-dihydro-5H-chromen-5-one derivatives 3a and 3b, respectively. The reaction of the latter compounds with cyanoacetylhydrazine gave the hydrazide-hydrazone derivatives 5a and 5b, respectively. Compounds 5a,b were used as the key starting materials for the synthesis of thiophen, coumarin, and pyridine derivatives. The newly synthesized compounds were evaluated against three human cancer cell lines, including HCT116 (colon carcinoma cell), MGC803 (gastric carcinoma cell), and Huh7 (hepatoma carcinoma cell). The results showed that 3b, 5b, 6b, 6d, 8b, 8c, 8d, 8f, 10b. 12a-h, 14a-d, 15a-h, and 16b-h displayed higher cytotoxic activity than 5-FU against HCT116 and MGC803 cell lines. Compounds 14d and 16f were the most promising compounds with IC50's 0.25 and 0.09 mu M against HCT116 cell line. The most potent compounds were selected for the in vitro against peripheral blood lymphocytes (PBL) from healthy donors. All compounds were practically devoid of significant cytotoxic activity in quiescent lymphocytes, with GI(50)'s of 42-68 mu M, while with the mitogenic stimulus phytohaemagglutinin (PHA), the GI(50)'s were reduced to about 20-32 mu M.