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

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

  • Sci Rep. 2025 May 28;15(1):18640. doi: 10.1038/s41598-025-02835-w.
Mateusz Kciuk 1,  Gabriela Machura 2,  Somdutt Mujwar 3,  Beata Marciniak 4,  Kamila Koszelska 2,  Sylwia Smarzewska 2,  Mariusz Mojzych 5,  Renata Kontek 4
Affiliations

Affiliations

  • 1 Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland. mateusz.kciuk@biol.uni.lodz.pl.
  • 2 Department of Inorganic and Analytical Chemistry, University of Lodz, 12 Tamka Str, 91-403, Lodz, Poland.
  • 3 Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
  • 4 Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland.
  • 5 The Mazovian Academy in Płock, Collegium Medicum, Plac Dąbrowskiego 2, 09-402, Plock, Poland.
PMID: 40436919 DOI: 10.1038/s41598-025-02835-w
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.

Keywords

Cancer; Drug; Pyrazole; Tetrazole; Triazine.

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