Title:Cytotoxicity and Anti-proliferative Properties of Heterocyclic Compounds Derived from Progesterone
Volume: 16
Issue: 8
Author(s): Rafat M. Mohareb, Nadia Y. Megally Abdo and Abeer A. Mohamed
Affiliation:
Keywords:
Progesterone, thiophene, pyran, pyridine, cytotoxicity, anti-proliferative.
Abstract: 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.
