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

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

  • Eur J Med Chem. 2019 Dec 15:184:111735. doi: 10.1016/j.ejmech.2019.111735.
Elmira Gibadullina 1,  Thi Thu Nguyen 2,  Anna Strelnik 3,  Anastasiia Sapunova 3,  Alexandra Voloshina 3,  Igor Sudakov 3,  Alexandra Vyshtakalyuk 3,  Julya Voronina 4,  Michael Pudovik 3,  Alexander Burilov 3
Affiliations

Affiliations

  • 1 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., 420088, Kazan, Russian Federation. Electronic address: gibadullina78@gmail.com.
  • 2 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., 420088, Kazan, Russian Federation; Kazan National Research Technological University, 68 K. Marx str., 420015, Kazan, Russia.
  • 3 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., 420088, Kazan, Russian Federation.
  • 4 N. S. Kurnakov Institute of General and Inorganic Chemistry, RAS, 31 Leninsky Av., 119991, Moscow, Russian Federation.
PMID: 31610378 DOI: 10.1016/j.ejmech.2019.111735
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.

Keywords

2,6-diaminopyridine; 3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidenemethylphosphonates; Cyclization; Cytotoxicity; Electrophilic substitution; Phosphonates; Sterically hindered phenols.

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