Synthesis, antibacterial and antitumor activity of methylpyridinium salts of pyridoxine functionalized 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles
Grigor’ev A. A., Shtyrlin N. V., Gabbasova R. R., Zeldi M. I., Yu. G. D., Gnezdilov O. I., Balakin K. V., Nasakin O. E., Shtyrlin Y. G.
Synthetic Communications
Vol.48, Issue17, P. 2288-2304
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1080/00397911.2018.1501487
Аннотация:
A library of 29 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles functionalized with a pyridoxine moiety was synthesized using a three-component one-pot reaction of aldehyde derivative of pyridoxine, malononitrile, and thiophenol. The obtained bipyridine structures were converted into methylpyridinium salts. Several compounds demonstrated expressed antibacterial activity with MICs (minimum inhibitory concentrations) in the range of 0.5–4 µg/mL against the three studied Gram-positive strains and 8–64 µg/mL against the Gram-negative E. coli strain, which was comparable or better than the activity of the reference antimicrobial agents. At the same time, all the synthesized compounds were inactive against the Gram-negative P. aeruginosa. Several compounds also demonstrated high cytotoxic activity against the studied tumor cells, but without selectivity for the normal HSF (human foreskin fibroblast) cells. Despite the preliminary character of the performed biological studies, the obtained res
Ключевые слова:
2-Amino-6-sulfanylpyridine-3,5-dicarbonitriles; antibacterial activity; antitumor activity; pyridoxine; quaternary ammonium salts
2 amino 4 (2 ethyl 8 methyl 4h [1, 3]dioxino[4,5 c]pyridin 5 yl) 6 (phenylthio)pyridine 3,5 dicarbonitrile; 2 amino 6 (phenylthio) 4 (2,2,8 trimethyl 4h [1,3]dioxino[4,5 c]pyridin 5 yl)pyridine 3,5 dicarbonitrile; 2 amino 6 sulfanylpyridine 3,5 dicarbonitrile derivative; 2 ethyl 8 methyl 4h [1,3]dioxino[4,5 c]pyridine 5 carbaldehyde; 2'amino 3',5'dicyano 5 hydroxy 4 (hydroxymethyl) 1,6 dimethyl 6'(phenylthio) [3,4'bipyridin] 1 ium bromide; 2'amino 5 hydroxy 4 (hydroxymethyl) 6 methyl 6'(phenylthio) [3,4'bipyridine] 3',5'dicarbonitrile; 5 hydroxymethyl 8 methyl 2 pentyl 4h [1,3]dioxino[4,5 c]pyridine; 5 [2 amino 3,5 dicyano 6 (phenylthio)pyridin 4 yl] 2 ethyl 7,8 dimethyl 4h [1,3]dioxino[4,5 c]pyridin 7 ium bromide; 5 [2 amino 3,5 dicyano 6 (phenylthio)pyridin 4 yl] 2,2,7,8 tetramethyl 4h [1,3]dioxino[4,5 c]pyridin 7 ium bromide; antibiotic agent; antineoplastic agent; benzalkonium chloride; doxorubicin; inorganic salt; methylpyridinium salt; miramistin; pyridoxine derivative; unclassif
Язык текста: Английский
ISSN: 1532-2432
Grigor’ev A. A.
Shtyrlin N. V.
Gabbasova R. R.
Zeldi M. I.
Yu. G. D. Grishaev D.
Gnezdilov O. I.
Balakin K. V. Konstantin Valeryevich 1970-
Nasakin O. E.
Shtyrlin Y. G.
Григор’ев А. А.
Штyрлин Н. В.
Габбасова Р. Р.
Зелди М. И.
Ю. Г. Д. Гришаев Д.
Гнездилов О. И.
Балакин К. В. Константин Валерьевич 1970-
Насакин О. Е.
Штyрлин Y. Г.
Synthesis, antibacterial and antitumor activity of methylpyridinium salts of pyridoxine functionalized 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles
Текст визуальный непосредственный
Synthetic Communications
Marcel Dekker Inc.
Vol.48, Issue17 P. 2288-2304
2018
Статья
2-Amino-6-sulfanylpyridine-3,5-dicarbonitriles antibacterial activity antitumor activity pyridoxine quaternary ammonium salts
2 amino 4 (2 ethyl 8 methyl 4h [1, 3]dioxino[4,5 c]pyridin 5 yl) 6 (phenylthio)pyridine 3,5 dicarbonitrile 2 amino 6 (phenylthio) 4 (2,2,8 trimethyl 4h [1,3]dioxino[4,5 c]pyridin 5 yl)pyridine 3,5 dicarbonitrile 2 amino 6 sulfanylpyridine 3,5 dicarbonitrile derivative 2 ethyl 8 methyl 4h [1,3]dioxino[4,5 c]pyridine 5 carbaldehyde 2'amino 3',5'dicyano 5 hydroxy 4 (hydroxymethyl) 1,6 dimethyl 6'(phenylthio) [3,4'bipyridin] 1 ium bromide 2'amino 5 hydroxy 4 (hydroxymethyl) 6 methyl 6'(phenylthio) [3,4'bipyridine] 3',5'dicarbonitrile 5 hydroxymethyl 8 methyl 2 pentyl 4h [1,3]dioxino[4,5 c]pyridine 5 [2 amino 3,5 dicyano 6 (phenylthio)pyridin 4 yl] 2 ethyl 7,8 dimethyl 4h [1,3]dioxino[4,5 c]pyridin 7 ium bromide 5 [2 amino 3,5 dicyano 6 (phenylthio)pyridin 4 yl] 2,2,7,8 tetramethyl 4h [1,3]dioxino[4,5 c]pyridin 7 ium bromide antibiotic agent antineoplastic agent benzalkonium chloride doxorubicin inorganic salt methylpyridinium salt miramistin pyridoxine derivative unclassif
A library of 29 2-amino-6-sulfanylpyridine-3,5-dicarbonitriles functionalized with a pyridoxine moiety was synthesized using a three-component one-pot reaction of aldehyde derivative of pyridoxine, malononitrile, and thiophenol. The obtained bipyridine structures were converted into methylpyridinium salts. Several compounds demonstrated expressed antibacterial activity with MICs (minimum inhibitory concentrations) in the range of 0.5–4 µg/mL against the three studied Gram-positive strains and 8–64 µg/mL against the Gram-negative E. coli strain, which was comparable or better than the activity of the reference antimicrobial agents. At the same time, all the synthesized compounds were inactive against the Gram-negative P. aeruginosa. Several compounds also demonstrated high cytotoxic activity against the studied tumor cells, but without selectivity for the normal HSF (human foreskin fibroblast) cells. Despite the preliminary character of the performed biological studies, the obtained res