title: Synthesis and biological evaluation of heterocyclic analogues of pregnenolone as novel anti-osteoporotic agents.
abstract: The structural modifications of pregnenolone have been described via the introduction of heterocyclic moieties at C-17 position by limiting the acyl group. Novel heterocyclic analogues of pregnenolone have been synthesized by using Friedlander and Claisen-Schmidt reactions, and the synthesized compounds were evaluated for their osteogenic activity. Among the synthesized derivatives, four compounds showed significantly increased ALP activity. Among all four active compounds, the novel compound 3a has shown significant bone matrix mineralization and mRNA expressions of osteogenic marker genes, BMP2, RUNX-2 and OCN at 1pM concentration.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Department of Chemistry, University of Allahabad, Allahabad 211001, India.
authors.forename: Saransh Wales
authors.initials: SW
authors.lastname: Maurya
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Dev
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Krishna Bhan
authors.initials: KB
authors.lastname: Singh
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Rai
authors.affiliation: Department of Chemistry, University of Allahabad, Allahabad 211001, India.
authors.forename: Ibadur Rahman
authors.initials: IR
authors.lastname: Siddiqui
authors.affiliation: Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: mauryarakesh@rediffmail.com.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
mesh_terms: D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy*; D011284:Pregnenolone / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D006571:Heterocyclic Compounds; D011284:Pregnenolone
keywords: ALP activity; Chalcone derivatives; Friedlander reaction; Osteoporosis; Pregnenolone