Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides.

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-05-28 DOI:10.1038/s41598-025-02835-w

Mateusz Kciuk, Gabriela Machura, Somdutt Mujwar, Beata Marciniak, Kamila Koszelska, Sylwia Smarzewska, Mariusz Mojzych, Renata Kontek

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引用次数: 0

Abstract

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides (MM-compounds) represent a novel class of heterocyclic compounds with promising anticancer potential. In this study, we report the synthesis and biological evaluation of two enantiomeric derivatives: the R-enantiomer (MM124) and the S-enantiomer (MM125). Both compounds exhibited potent and selective cytotoxicity against a panel of cancer cell lines derived from various tissue types, with a median IC₅₀ value of 0.35 µM. Mechanistic investigations in colorectal (HT-29) and prostate (PC-3) cancer cell lines demonstrated that the compounds induce apoptosis, oxidative stress, and DNA damage. Electrochemical assays and computational studies further suggested that MM124 and MM125 interact with DNA. Additionally, in silico pharmacokinetic and toxicological profiling indicated favorable drug-like properties. These findings support the potential of MM124 and MM125 as candidates for the development of new anticancer agents, warranting further structural optimization and preclinical evaluation.

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新型手性吡唑[4,3-e]四唑[1,5-b][1,2,4]三嗪类磺胺类化合物的合成、抗癌评价及电化学研究。

吡唑[4,3-e]四唑[1,5-b][1,2,4]三嗪磺胺类化合物是一类具有抗癌潜力的新型杂环化合物。在本研究中，我们报道了两种对映体衍生物的合成和生物学评价：r -对映体（MM124）和s -对映体（MM125）。这两种化合物对来自各种组织类型的癌细胞系都表现出有效和选择性的细胞毒性，IC₅0的中位数为0.35µM。在结直肠癌（HT-29）和前列腺癌（PC-3）细胞系中进行的机制研究表明，这些化合物可诱导细胞凋亡、氧化应激和DNA损伤。电化学分析和计算研究进一步表明MM124和MM125与DNA相互作用。此外，在硅药代动力学和毒理学分析显示有利的药物样性质。这些发现支持MM124和MM125作为开发新的抗癌药物的候选物的潜力，需要进一步的结构优化和临床前评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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