Structural, computational and anticancer activity studies of D-seco-17-mesyloxy androstane derivatives

• Published in: Journal of molecular structure 2019-07, Vol.1187, p.14-22
• Main Authors: Oklješa, Aleksandar, Klisurić, Olivera R., Jakimov, Dimitar, Penov Gaši, Katarina, Sakač, Marija, Jovanović-Šanta, Suzana
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Def2-TZVP; DFT; PW6B95; Sulfonates; X-ray
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2019.03.055

Sulfonates express a variety of biological and pharmacological activities, which indicates them as compounds of interest, in both synthetic and biological research areas. Among sulfonates, mesylates (methanesulfonyloxy compounds) draw attention by their physicochemical and biological properties, as well as by their reactivity. Here we present X-ray and computational study of 3β-acetoxy-17-methanesulfonyloxy-16,17-secoandrost-5-ene-16-nitrile (1) and its anti-proliferative activity against five common human cancer cell lines. Computational study includes geometry optimization, frontier molecular orbital analysis and molecular electrostatic potential mapping at the PW6B95-D3BJ/Def2-TZVP level of theory. Studied mesylate compound 1 expressed quite strong selective anti-proliferative effect against human breast and prostate cancer cell lines. Anticancer activity of this compound was compared to its 17-methyl analogs (compounds 2 and 3). Computational study of d-secoandrostane compounds 1–3 allowed us to presume the structural features, important for their chemical reactivity. The differences between the antiproliferative activity of d-secomesylate compound 1 and its 17-methyl analogs 2 and 3 could be explained by possible mechanism in the cancer cells. [Display omitted] •X-ray and computational study of d-secoandrostane mesylate (1) were performed.•Computational study of its 17-methyl analogs 2 (17S-) and 3 (17R-) was conducted.•PW6B95-D3BJ/Def2-TZVP used for geometry optimization, HOMO/LUMO and MEP analyses.•Anticancer activity of d-secoandrostane compounds 1–3 was tested.•Structural features important for chemical or biological activity were studied.