Synthesis and biological evaluation of new substituted thioglycolurils, their analogues and derivatives

Synthesis and biological evaluation of new substituted thioglycolurils, their analogues and derivatives Научная публикация

Журнал

European Journal of Medicinal Chemistry
ISSN: 1768-3254 , E-ISSN: 0223-5234

Вых. Данные

Год: 2017, Том: 140, Страницы: 141-154 Страниц : 14 DOI: 10.1016/j.ejmech.2017.09.009

Авторы

Gazieva Galina A. ¹ , Anikina Lada V. ² , Nechaeva Tatyana V. ^3,1 , Pukhov Sergey A. ² , Karpova Tatyana B. ¹ , Popkov Sergey V. ³ , Nelyubina Yulia V. ⁴ , Kolotyrkina Natalya G. ¹ , Kravchenko Angelina N. ¹

Организации

1	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation
2	Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation
3	D. Mendeleev University of Chemical Technology of Russia, Moscow 125047, Russian Federation
4	A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow 119991, Russian Federation

A novel series of substituted N-aminothioglycolurils was synthesized by tandem hydrazone formation – ring contraction reaction of 3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (E)-3-phenyl(furan-2-yl)acrylaldehyde derivatives. S-Alkyl substituted N-aminothioglycolurils were prepared through alkylation of corresponding thioglycolurils with iodoalkane or 4-chlorobenzylchloride. Methylthio group in S-methyl derivatives can be substituted with hydroxyl group in acid medium to give N-aminoglycolurils. Representative compounds were evaluated for their cytotoxic activity against RD, A549, HCT116 and MCF7 human cancer cell lines by MTT-assay and screened for their antifungal activity against phytopathogenic fungi using the mycelium growth inhibition method in vitro. Among the derivatives, 4-((E)-((E)-3-(2-Methoxyphenyl)allylidene)amino)-3-methyl-1-phenylthioglycoluril 8i was found to have the highest antiproliferative activity toward the RD and HCT116 cell lines (8i: IC50 = 0.02 and 0.012 μM, respectively), which exceeded cytotoxicity of reference drugs. 1,3-Diethyl-4-((E)-((E)-3-(2-methoxyphenyl)allylidene)amino)thioglycoluril 8l showed the most marked activity toward A549 cells (8l: IC50 = 0.61 μM) compared to reference drugs. The IC50 values of thioglycolurils 8i,l against normal human embryonic kidney cells HEK293 were 0.23 and 86.11 μM, respectively, exceeding the IC50 values of this compound toward the RD, HCT116 (8i) and A549 cells (8l) by one-two orders of magnitude. Experiments with annexin showed that compounds 8b,i,l induced apoptosis in Jurkat cells (acute T cell leukemia). Alkylthioderivatives 12a,13a displayed the strongest antifungal action against R. solani, F. oxysporum, and F. moniliforme exceeding those of triadimefon.

Gazieva G.A. , Anikina L.V. , Nechaeva T.V. , Pukhov S.A. , Karpova T.B. , Popkov S.V. , Nelyubina Y.V. , Kolotyrkina N.G. , Kravchenko A.N.
Synthesis and biological evaluation of new substituted thioglycolurils, their analogues and derivatives
European Journal of Medicinal Chemistry. 2017. V.140. P.141-154. DOI: 10.1016/j.ejmech.2017.09.009 WOS Scopus OpenAlex

≡ Web of science:	WOS:000414620000013
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