Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides
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 th...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-02835-w |
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| author | Mateusz Kciuk Gabriela Machura Somdutt Mujwar Beata Marciniak Kamila Koszelska Sylwia Smarzewska Mariusz Mojzych Renata Kontek |
| author_facet | Mateusz Kciuk Gabriela Machura Somdutt Mujwar Beata Marciniak Kamila Koszelska Sylwia Smarzewska Mariusz Mojzych Renata Kontek |
| author_sort | Mateusz Kciuk |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2ba1272df32241e3b2b0bb41fcdd1c3c |
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| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2ba1272df32241e3b2b0bb41fcdd1c3c2025-08-20T01:59:57ZengNature PortfolioScientific Reports2045-23222025-05-0115112410.1038/s41598-025-02835-wSynthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamidesMateusz Kciuk0Gabriela Machura1Somdutt Mujwar2Beata Marciniak3Kamila Koszelska4Sylwia Smarzewska5Mariusz Mojzych6Renata Kontek7Department of Molecular Biotechnology and Genetics, University of LodzDepartment of Inorganic and Analytical Chemistry, University of LodzChitkara College of Pharmacy, Chitkara UniversityDepartment of Molecular Biotechnology and Genetics, University of LodzDepartment of Inorganic and Analytical Chemistry, University of LodzDepartment of Inorganic and Analytical Chemistry, University of LodzThe Mazovian Academy in Płock, Collegium MedicumDepartment of Molecular Biotechnology and Genetics, University of LodzAbstract 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.https://doi.org/10.1038/s41598-025-02835-wCancerDrugPyrazoleTetrazoleTriazine |
| spellingShingle | Mateusz Kciuk Gabriela Machura Somdutt Mujwar Beata Marciniak Kamila Koszelska Sylwia Smarzewska Mariusz Mojzych Renata Kontek Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides Scientific Reports Cancer Drug Pyrazole Tetrazole Triazine |
| title | Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides |
| title_full | Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides |
| title_fullStr | Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides |
| title_full_unstemmed | Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides |
| title_short | Synthesis, anticancer evaluation, and electrochemical investigation of new chiral pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides |
| title_sort | synthesis anticancer evaluation and electrochemical investigation of new chiral pyrazolo 4 3 e tetrazolo 1 5 b 1 2 4 triazine sulfonamides |
| topic | Cancer Drug Pyrazole Tetrazole Triazine |
| url | https://doi.org/10.1038/s41598-025-02835-w |
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