Synthesis, cytotoxicity against cancer and normal cell lines of novel hydrazide –hydrazone derivatives bearing 5H-chromen-5-one

AbstractThe reaction of cyclohexan-1,3-dione with either of malononitrile or ethyl cyanoacetate gave the 4-amino-6,7-dihydro-5H-chromen-5-one derivatives3a and3b, respectively. The reaction of the latter compounds with cyanoacetylhydrazine gave the hydrazide –hydrazone derivatives5a and5b, respectively. Compounds5a,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 that3b,5b,6b,6d,8b,8c,8d,8f,10b.12a –h,14a –d,15a –h, and16b –h displayed higher cytotoxic activity than 5-FU against HCT116 and MGC803 cell lines. Compounds14d and16f were the most promising compounds with IC50’s 0.25 and 0.09 μM 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 GI50’s of 42–68 μM, while with the mitogenic stimulus phytohaemagglutinin (PHA), the GI50’s were reduced to about 20–32 μM.

Source: Medicinal Chemistry Research - October 10, 2019 Category: Chemistry Source Type: research