New 2,6-diaminopyridines containing a sterically hindered benzylphosphonate moiety in the aromatic core as potential antioxidant and anti-cancer drugs...

ID: ALA4311994

Journal: Eur J Med Chem

Title: New 2,6-diaminopyridines containing a sterically hindered benzylphosphonate moiety in the aromatic core as potential antioxidant and anti-cancer drugs.

Authors: Gibadullina E, Nguyen TT, Strelnik A, Sapunova A, Voloshina A, Sudakov I, Vyshtakalyuk A, Voronina J, Pudovik M, Burilov A.

Abstract: A series of 2,6-diaminopyridines was synthesized for the first time, containing phosphoryl sterically hindered phenolic fragments in the aromatic core. The antioxidant activity of these compounds was investigated, 2,6-diaminopyridine derivatives were shown to exhibit higher activity in comparison with their structural analogues. For dialkyl/diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonates, their structural analogues based on meta-phenylenediamine, phosphorus-containing sterically hindered phenols and the corresponding cyclohexadienones cytotoxicity against tumor lines of epithelioid carcinoma of the cervix uteri (M-Hela) and breast adenocarcinoma (MCF-7) has been studied in vitro, as well as on normal human Chang liver cell lines. Diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonate was shown to be the most active against the epithelioid line M-Hela - IC50 comprises 7.4 μM. It was shown that apoptosis induced by the lead compound proceeds along the internal pathway of caspase-9 activation. It was established that all studied compounds do not possess hemolytic activity.

CiteXplore: 31610378

DOI: 10.1016/j.ejmech.2019.111735

Patent ID: ┄