title: Biological activity and conformational analysis of C20 and C14 epimers of CD-ring modified trans-decalin 1alpha,25-dihydroxyvitamin D analogs.
abstract: In the context of our ongoing study of vitamin D structure-function relationships and in an attempt to obtain a better dissociation of their prodifferentiating (HL-60) and/or antiproliferative (MCF-7) activities and their calcemic activity, further 20-epi and 14-epi modifications were made to three trans-decalin CD-ring analogs of 1,25-dihydroxyvitamin D(3), the hormonally active metabolite of vitamin D(3), possessing a natural 20R side chain and featuring additional structural modifications in the seco-B-ring and in the A-ring. Following a previously observed trend and in agreement with the conformational analysis results, all three 20-epi derivatives show substantially lower biological activities, opposite to what is usually observed for analogs having the natural CD-ring. The 14-epi modification (cis-decalins) has little effect on the biological activity of the ynediene type and the saturated derivative, but results in an approximate 10-fold reduction in activity of the previtamin derivative. No better dissociation of the prodifferentiating and/or antiproliferative activities and the calcemic activity was achieved.
authors.affiliation: Laboratory for Organic Synthesis, Department of Organic Chemistry, Ghent University, Krijgslaan 281 (S4), B-9000 Gent, Belgium. pierre.declercq@UGent.be
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: De Clercq
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Murad
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Gao
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Haver
authors.forename: Maurits
authors.initials: M
authors.lastname: Vandewalle
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.forename: Lieve
authors.initials: L
authors.lastname: Verlinden
authors.forename: Christel
authors.initials: C
authors.lastname: Verboven
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D013057:Spectrum Analysis
chemical_list: D002117:Calcitriol