title: Antihormonal potential of selected D-homo and D-seco estratriene derivatives.
abstract: Since many estrogen derivatives exhibit anti-hormone or enzyme inhibition potential, a large number of steroidal derivatives have been synthesised from appropriate precursors, in order to obtain potential therapeutics for the treatment of hormone-dependent cancers. In molecular docking studies, based on X-ray crystallographic analysis, selected D-homo and D-seco estratriene derivatives were predicted to bind strongly to estrogen receptor α (ERα), aromatase and 17,20 lyase, suggesting they could be good starting compounds for antihormonal studies. Test results in vivo suggest that these compounds do not possess estrogenic activity, while some of them showed weak anti-estrogenic properties. In vitro anti-aromatase and anti-lyase assays showed partial inhibition of these two enzymes, while some compounds activated aromatase. Aromatase activators are capable of promoting estrogen synthesis for treatment of pathological conditions caused by estrogen depletion, e.g. osteopenia or osteoporosis.
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: suzana.jovanovic-santa@dh.uns.ac.rs.
authors.forename: Suzana S
authors.initials: SS
authors.lastname: Jovanović-Šanta
authors.affiliation: Department of Biology and Ecology, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Petri
authors.affiliation: Department of Physics, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 4, 21000 Novi Sad, Serbia.
authors.forename: Olivera R
authors.initials: OR
authors.lastname: Klisurić
authors.affiliation: First Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Szécsi
authors.affiliation: Department of Biology and Ecology, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia.
authors.forename: Radmila
authors.initials: R
authors.lastname: Kovačević
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
authors.forename: Julijana A
authors.initials: JA
authors.lastname: Petrović
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004963:Estrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006718:Homosteroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D012632:Secosteroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D004967:Estrogens; D006718:Homosteroids; D006727:Hormone Antagonists; D012632:Secosteroids; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase
keywords: 16,17-Seco-estratriene derivatives; Antiestrogens; D-homo-estratriene derivatives; Molecular docking studies; Steroidogenesis enzymes inhibitors and activators; X-ray (XRD)