X-Ray Crystal Structure of 10β-Hydroxy-4β,5β-epoxyestr-1-en-3,17-dione and Antitumor Activity of its Congeners

• Published in: Molecules (Basel, Switzerland) Vol. 4; no. 12; pp. 338 - 352
• Main Authors: Bogdan A. Ã…Â olaja, Miroslav J. GaÅ¡ić, Zorica Juranić, Marianne Strümpel, Bela Ribar, Borislava Markov, AgneÅ¡ Kapor, Dragana R. Milić
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.11.1999
• Subjects: antitumor activity; epoxyquinol; quinol; Steroids; X-ray crystallography
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/41200338

Based on the biological properties of epoxyquinols from natural sources, the title compound was synthesised as a potential antitumor agent. Its molecular structure was partially confirmed by NMR studies. The detailed structure was established by X-ray analysis revealing two symmetry independent molecules in the asymmetric unit each consisting of four fused rings with the C(10) β-oriented hydroxy group and β-oriented O atom bridging C(4) and C(5). The conformation of A ring in both conformers A and B is boat (B3,6), while rings B and C are chairs (1C4) and the five-membered D ring is in an envelope (E2) conformation. The in vitro antitumor activity of title compound and its 17b-acetoxy analogue against HeLa and Fem-x cells revealed IC50 values of 5.7 and 7.1 mM, and 2.25 and 1.58 mM, respectively. Corresponding quinols were tested on 47 cell lines with 10b-hydroxy-17β-acetoxyestra-1,4-dien-3-one being most active against leukemia SR cells (GI50 = 0.17 mM).