TY - JOUR

T1 - Synthesis and biological evaluation of 1,2,4-triazoloazines as potent anticancer agents

AU - Serebrennikova, Polina O.

AU - Paznikova, Julia A.

AU - Kirnos, Eva Andreyevna

AU - Utepova, Irina A.

AU - Kazakova, Elizaveta D.

AU - Lazarev, Vladimir F.

AU - Kuznetcova, Liubov S.

AU - Margulis, Boris A.

AU - Guzhova, Irina V.

AU - Chupakhin, Oleg N.

AU - Sarapultsev, Alexey P.

N1 - This study was funded by the Russian Science Foundation, grant No. 22-13-00298 and Ministry of Science and Education of the Russian Federation, State Contract no. FENU-2023-0014.

PY - 2023

Y1 - 2023

N2 - The present study successfully synthesized 16 new derivatives of mono- and bis-1,2,4-triazoloazines through the condensation of mono- and dihydrazinylazines with (heteroaryl)carbaldehydes 6 followed by the oxidative cyclization of mono- and bis-azinylhydrazones in the presence of hypervalent iodine(iii). The yields of these compounds ranged from 14% to 84%. The structural identification of the synthesized compounds was confirmed by elemental analyses, infrared spectroscopy (IR), and proton and carbon nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR) and mass spectrometry. The cytotoxic activity of the compounds 8, 12, and 14 obtained was evaluated against the cancer cell lines MCF7, DLD-1, and A549. Furthermore, the selectivity of the toxic effect of these triazoloazines on human dermal fibroblasts (DF-2) was studied. The semilethal concentration of each compound was determined after 24 hours of incubation for each cell line. The results showed that some of the new mono- and bis-1,2,4-triazoloazine derivatives exhibited significant toxicity towards tumor cells while having minimal effects on normal non-tumor fibroblasts. This selective cytotoxicity suggests the potential of these compounds as anticancer agents with reduced side effects on healthy cells. The new derivatives of mono- and bis-1,2,4-triazoloazines were obtained. The cytotoxic activity of the compounds was evaluated against the cancer cell lines.

AB - The present study successfully synthesized 16 new derivatives of mono- and bis-1,2,4-triazoloazines through the condensation of mono- and dihydrazinylazines with (heteroaryl)carbaldehydes 6 followed by the oxidative cyclization of mono- and bis-azinylhydrazones in the presence of hypervalent iodine(iii). The yields of these compounds ranged from 14% to 84%. The structural identification of the synthesized compounds was confirmed by elemental analyses, infrared spectroscopy (IR), and proton and carbon nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR) and mass spectrometry. The cytotoxic activity of the compounds 8, 12, and 14 obtained was evaluated against the cancer cell lines MCF7, DLD-1, and A549. Furthermore, the selectivity of the toxic effect of these triazoloazines on human dermal fibroblasts (DF-2) was studied. The semilethal concentration of each compound was determined after 24 hours of incubation for each cell line. The results showed that some of the new mono- and bis-1,2,4-triazoloazine derivatives exhibited significant toxicity towards tumor cells while having minimal effects on normal non-tumor fibroblasts. This selective cytotoxicity suggests the potential of these compounds as anticancer agents with reduced side effects on healthy cells. The new derivatives of mono- and bis-1,2,4-triazoloazines were obtained. The cytotoxic activity of the compounds was evaluated against the cancer cell lines.

UR - https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=tsmetrics&SrcApp=tsm_test&DestApp=WOS_CPL&DestLinkType=FullRecord&KeyUT=001069753100001

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85173812405

U2 - 10.1039/d3nj03158f

DO - 10.1039/d3nj03158f

M3 - Article

VL - 47

SP - 18325

EP - 18331

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

IS - 39

ER -