Pregnenolone derivatives as potential anticancer agents

Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring-D modification of 1 resulted in the synthesis of benzylidenes 2-17, pyrazolines 18-76, pyrazoles 85-91, hydrazones 77-84, and oximes 92-107 derivatives. The structure of compound 107 was also deduced through single crystal X-ray diffraction studies. The inclusion of furanyl and pyridyl rings to pregnenolone skeleton increases the cytotoxicity of all compounds significantly. Among benzylidene derivatives, only heterocyclic enone 8 (IC50 = 0.74 mu M/mL against HepG2), and 17 (IC50 = 4.49 mu M/mL against HepG2, IC50 = 5.01 mu M/mL against MDA-MB-230 cancer cell line) exhibited a significant activity. The cytotoxicity data of pyrazoline derivatives 18-76 revealed that only furanyl bearing pyrazolines 40,42-44,48, and 49 exhibited significant activities. While all (O-carboxymethyl) oximes, hydazones, and pyrazoles derivatives of pregnenolone did not show any significant activity against both the cell lines. Thus the furanyl bearing enone 8 (IC50 = 0.74 mu M/mL against HepG2), and its pyrazoline derivative 48 (IC50 = 0.91 mu M/mL against MDA-MB-230 cancer cell lines) were identified as the most active compounds in all derivatives of pregnenolone. (C) 2011 Elsevier Inc. All rights reserved.