Cytotoxicity and Anti-proliferative Properties of Heterocyclic Compounds Derived from Progesterone.

The following study explored the cytotoxic effect on human cancer cells of a series of novel progesterone derivatives through the synthesis of heterocyclic compounds incorporating progesterone moiety. The reaction of progesterone (1) with cyanoacetanilide derivatives gave the condensation products 3a,b. Either of compound 3a or 3b reacted with elemental sulfur affording the thiophene derivatives 4a and 4b, respectively. In addition, progesterone (1) underwent some multi-component reactions with aromatic aldehydes and cyanomethylene reagents in triethylamine to give the pyran derivatives 10a-f. Carrying the same reactions but using ammonium acetate afforded the pyridine derivatives 11a-f. The anti-tumor evaluations of the newly synthesized products were tested against six human cancer and normal cell lines. The results showed that nine compounds (3b, 7c, 10b, 10d, 10f, 11d, 13a, 13b and 14b) revealed optimal cytotoxic effect against cancer cell lines with IC50 ˂ 550 nM and their cytotoxicity's were higher than that of progesterone. Moreover, the toxicity of the most active compounds was measured against shrimp larvae. In addition, the anti-proliferative evaluations of these potent compounds were measured.