Synthesis and anti-aromatase activity of some new steroidal D-lactones

• Published in: Steroids Vol. 70; no. 1; pp. 47 - 53
• Main Authors: Gaši, Katarina M. Penov, Stojanović, Srdjan Z., Sakač, Marija N., Popsavin, Mirjana, Šanta, Suzana Jovanović, Stanković, Slobodanka M., Klisurić, Olivera R., Andrić, Nebojša, Kovačević, Radmila
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 2005; Elsevier; Elsevier Science
• Subjects: Androgens; Animals; Aromatase inhibitors; Aromatase Inhibitors - chemical synthesis; Aromatase Inhibitors - chemistry; Aromatase Inhibitors - pharmacology; Biochemistry & Molecular Biology; Biological and medical sciences; Endocrinology & Metabolism; Female; Fundamental and applied biological sciences. Psychology; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Rats; Science & Technology; Spectrophotometry, Infrared; Steroidal D-lactones; Steroids - chemistry; Vertebrates: endocrinology; X-ray analysis; Androgens; X-ray analysis; Steroidal D-lactones; Aromatase inhibitors; steroidal D-lactones; aromatase inhibitors; INHIBITION; androgens; Androgen; Enzyme; Biosynthesis; X ray; Estrogen synthase; Sex steroid hormone
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2004.10.005

Starting from D-seco derivatives of 5-androstene 1– 3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil), the corresponding D-lactones 6– 12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis. Anti-aromatase assay showed that tested compounds possess inhibition potency, however, two to four times smaller (IC 50 from 0.2 to 0.7 μM, respectively) in comparison to aminoglutethimide (AG).