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Synthesis, modification and cytotoxic properties of new 7-amino-5-arylazolo[1,5-a]pyrimidine-6-carbonitriles

Ilya I. Butorin, Vsevolod V. Melekhin, Denis D. Chirkov, Maria D. Tokhtueva, Andrey A. Zonov, Olga A. Konovalova, Elena A. Fesenko, Anna E. Chernysheva, Pavel A. Slepukhin, Svetlana K. Kotovskaya, Vladimir L. Rusinov

Abstract


Azolo[1,5-a]pyrimidine is one of the most promising scaffold in the development of potent anticancer agents. However, the structural motifs in such development are often limited to 5,7-substituted azolo[1,5-a]pyrimidines due to the well-known synthesis route and existing drugs (e.g., Dinaciclib) on their basis. To expand the understanding of rare substituent combinations in this research field, a new series of 7-amino-5-aryl-6-cyanoazolo[1,5-a]pyrimidines with various azole moieties were synthesized and studied on A172, Rd, Hos and HEK293 cell lines. The obtained derivatives were further modified by acylation to introduce an additional pharmacophore moiety. During the study of anticancer activity, compounds with a pronounced cytotoxic effect were found. The analysis of activity against the embryonal rhabdomyosarcoma (Rd) cell line suggested a mechanism of cytotoxic action causing a significant decrease in mitochondrial potential in neoplastic cells.

Keywords


azolo[1,5-a]pyrimidine, Michael reaction, cancer, MTT, sarcoma, rhabdomyosarcoma, azoloazine

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DOI: https://doi.org/10.15826/chimtech.2025.12.2.02

Copyright (c) 2024 Ilya I. Butorin, Vsevolod V. Melekhin, Denis D. Chirkov, Maria D. Tokhtueva, Andrey A. Zonov, Olga A. Konovalova, Elena A. Fesenko, Anna E. Chernysheva, Pavel A. Slepukhin, Svetlana K. Kotovskaya, Vladimir L. Rusinov

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