Synthesis of 1,3-dialkylthioselenoglycolurils - novel antifungal agents

Synthesis of 1,3-dialkylthioselenoglycolurils - novel antifungal agents Full article

Journal

Tetrahedron
ISSN: 0040-4020 , E-ISSN: 1464-5416

Output data

Year: 2025, Volume: 187, Article number : 134947, Pages count : DOI: 10.1016/j.tet.2025.134947

Authors

Baranov Vladimir V. ¹ , Galochkin Anton A. ¹ , Alekseenko Anna L. ² , Popkov Sergei V. ² , Kolotyrkina Natalya G. ¹ , Nelyubina Yulia V. ³ , Globa Anastasiya A. ⁴ , Kravchenko Angelina N. ¹ , Fershtat Leonid L. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., Moscow, 119991, Russian Federation
2	Mendeleev University of Chemical Technology, 9 Miusskaya Sq., Moscow, 125047, Russian Federation
3	Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Ac. Semenov Pr., 1, Chernogolovka, 142432, Moscow region, Russian Federation
4	Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences, Institute of Physiologically Active Compounds, Severny Proezd, 1, Chernogolovka, Moscow region, 142432, Russian Federation

A two-step synthesis of pharmacologically relevant 1,3-dialkyl-5-selenoxohexahydroimidazo[4,5-d]imidazole-2(1H)-thiones (thioselenoglycolurils) starting from readily available thioglycolurils was realized for the first time. The developed protocol involves S-methylation of initial thioglycolurils followed by selenation of thus formed isothiouronium salts with NaHSe generated in situ from grey Se and NaBH4. In vitro study of antifungal activity against Sclerotinia sclerotiorum, Fusarium oxysporum, Fusarium maniliforme, Bipolaris sorokiniana, Venturia inaequalis, Rhizoctonia solani phytopathogens and yeasts Candida albicans and Cryptococcus neoformans, Candida auris, MDR Candida auris, Candida glabrata was performed. It was found that 8 thioselenoglycolurils completely inhibited the growth of V. inaequalis and R. solani fungi and partially suppress the growth of B. sorokiniana fungus (MGI 59–67 %) analogous to triadimefon (MGI 68 %). Effective antifungal action towards C. albicans and C. neoformans (MIC ≤ 0.25 μg/mL) with no discernible toxicity against mamallian cells was revealed for 4 representatives of thioselenoglycolurils. Effective growth inhibition of gram-positive bacterium S. aureus, yeast C. neoformans, C. auris, MDR C. auris, C. glabrata was additionally noted for 1,3-diethylthioselenoglycoluril. Moreover, the latter compound has low toxicity (LD50 = 129 mg/kg) and can be referred to as a lead candidate for the development of new antifungal pharmaceuticals.

Baranov V.V. , Galochkin A.A. , Alekseenko A.L. , Popkov S.V. , Kolotyrkina N.G. , Nelyubina Y.V. , Globa A.A. , Kravchenko A.N. , Fershtat L.L.
Synthesis of 1,3-dialkylthioselenoglycolurils - novel antifungal agents
Tetrahedron. 2025. V.187. 134947 . DOI: 10.1016/j.tet.2025.134947 WOS Scopus OpenAlex

Web of science:	WOS:001576662200001
Scopus:	2-s2.0-105016353141
OpenAlex:	W4414268076

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