Preparation of Novel Pyrazolo[4,3- e]tetrazolo[1,5- b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Mateusz Kciuk; Somdutt Mujwar; Anna Szymanowska; Beata Marciniak; Karol Bukowski; Mariusz Mojzych; Renata Kontek

doi:10.3390/ijms23115892

Preparation of Novel Pyrazolo[4,3- e]tetrazolo[1,5- b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies

Int J Mol Sci. 2022 May 24;23(11):5892. doi: 10.3390/ijms23115892.

Authors

Mateusz Kciuk^{1

2}, Somdutt Mujwar³, Anna Szymanowska⁴, Beata Marciniak¹, Karol Bukowski¹, Mariusz Mojzych⁴, Renata Kontek¹

Affiliations

¹ Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland.
² Doctoral School of Exact and Natural Sciences, University of Lodz, 90-237 Lodz, Poland.
³ M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University) Mullana, Ambala 133207, India.
⁴ Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland.

Abstract

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides constitute a novel class of heterocyclic compounds with broad biological activity, including anticancer properties. Investigated in this study, MM-compounds (MM134, MM136, MM137, and MM139) exhibited cytotoxic and proapoptotic activity against cancer cell lines (BxPC-3, PC-3, and HCT-116) in nanomolar concentrations without causing cytotoxicity in normal cells (L929 and WI38). In silico predictions indicate that tested compounds exhibit favorable pharmacokinetic profiles and may exert anticancer activity through the inhibition of BTK kinase, the AKT-mTOR pathway and PD1-PD-L1 interaction. Our findings point out that these sulfonamide derivatives may constitute a source of new anticancer drugs after optimization.

Keywords: apoptosis; cancer cells; cytotoxicity; pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine; sulfonamides.

MeSH terms

Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Cell Proliferation
Drug Screening Assays, Antitumor
Molecular Structure
Structure-Activity Relationship
Sulfonamides* / pharmacology
Triazines / pharmacology

Substances

Antineoplastic Agents
Sulfonamides
Triazines

Grants and funding

This research received no external funding.