Antihormonal potential of selected D-homo and D-seco estratriene derivatives

• Published in: Steroids Vol. 97; pp. 45 - 53
• Main Authors: Jovanović-Šanta, Suzana S., Petri, Edward T., Klisurić, Olivera R., Szécsi, Mihály, Kovačević, Radmila, Petrović, Julijana A.
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.05.2015; Elsevier
• Subjects: 16,17-Seco-estratriene derivatives; Animals; Antiestrogens; Aromatase - metabolism; Biochemistry & Molecular Biology; Crystallography, X-Ray; D-homo-estratriene derivatives; Dose-Response Relationship, Drug; Endocrinology & Metabolism; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Estrenes - chemical synthesis; Estrenes - chemistry; Estrenes - pharmacology; Estrogens - biosynthesis; Female; Homosteroids - chemical synthesis; Homosteroids - chemistry; Homosteroids - pharmacology; Hormone Antagonists - chemical synthesis; Hormone Antagonists - chemistry; Hormone Antagonists - pharmacology; Life Sciences & Biomedicine; Models, Molecular; Molecular Conformation; Molecular docking studies; Rats; Rats, Wistar; Science & Technology; Secosteroids - chemical synthesis; Secosteroids - chemistry; Secosteroids - pharmacology; Stereoisomerism; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Steroid 17-alpha-Hydroxylase - metabolism; Steroidogenesis enzymes inhibitors and activators; Structure-Activity Relationship; X-ray (XRD); Molecular docking studies; Steroidogenesis enzymes inhibitors and activators; 16,17-Seco-estratriene derivatives; Antiestrogens; D-homo-estratriene derivatives; X-ray (XRD); BREAST-CANCER; PLATFORM; BIOLOGICAL-ACTIVITY; RECEPTOR; AROMATASE INHIBITORS; 17-ALPHA-HYDROXYLASE/C-17,C-20-LYASE
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2014.08.026

•New D-homo and 16,17-seco-estratriene compounds were synthesised and characterized.•Docking studies were performed for protein targets of steroidal anti-cancer drugs.•Estrogen and antiestrogen activity of the new compounds was determined.•X-ray structural analysis of a new compound was performed.•Some compounds partially inhibit 17,20 lyase, while some activated aromatase. 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.