title: Pregnenolone derivatives as potential anticancer agents.
abstract: 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 μM/mL against HepG2), and 17 (IC50=4.49 μM/mL against HepG2, IC50=5.01 μM/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 μM/mL against HepG2), and its pyrazoline derivative 48 (IC50=0.91 μM/mL against MDA-MB-230 cancer cell lines) were identified as the most active compounds in all derivatives of pregnenolone.
authors.affiliation: H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan.
authors.forename: M
authors.initials: M
authors.lastname: Iqbal Choudhary
authors.forename: M
authors.initials: M
authors.lastname: Shahab Alam
authors.lastname: Atta-Ur-Rahman
authors.forename: Sammer
authors.initials: S
authors.lastname: Yousuf
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: An-Shen
authors.initials: AS
authors.lastname: Lin
authors.forename: F
authors.initials: F
authors.lastname: Shaheen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011284:Pregnenolone