Abstract
A simple one-pot Prins–Ritter route was developed for the synthesis of 16-acylamino-17a-hydroxy-d-homoestrone 3-benzyl and 3-methyl ethers in the 13α-estrone series. The d-secosteroidal δ-alkenyl-aldehydes were allowed to react with different nitriles in the presence of BF3·OEt2 as a Lewis acid catalyst. Prins cyclizations afforded 17a-hydroxy-16-carbenium ions, which underwent Ritter reactions with nitriles, leading to 16α- or 16β-acylamino derivatives. A side-product in which a dihydro-1,3-oxazine was bridged to six-membered ring D at positions 16α,17aα was formed in each reaction. The antiproliferative properties of the novel 13α-d-homosteroids were determined on a panel of human adherent cancer cell lines (HeLa, MCF-7, T47D, MDA-MB-231, MDA-MB-361, A2780 and A431) by means of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays. Some compounds proved to be more effective (with submicromolar IC50 values) than the reference agent cisplatin. One of the most potent compounds substantially increased the rate of tubulin polymerization. Cell cycle analyses by flow cytometry indicated a concentration-dependent accumulation of the G2/M cell population.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
