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

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 agai...

Descripción completa

Detalles Bibliográficos
Autores principales: Kciuk, Mateusz, Mujwar, Somdutt, Szymanowska, Anna, Marciniak, Beata, Bukowski, Karol, Mojzych, Mariusz, Kontek, Renata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180621/
https://www.ncbi.nlm.nih.gov/pubmed/35682571
http://dx.doi.org/10.3390/ijms23115892
_version_ 1784723565396885504
author Kciuk, Mateusz
Mujwar, Somdutt
Szymanowska, Anna
Marciniak, Beata
Bukowski, Karol
Mojzych, Mariusz
Kontek, Renata
author_facet Kciuk, Mateusz
Mujwar, Somdutt
Szymanowska, Anna
Marciniak, Beata
Bukowski, Karol
Mojzych, Mariusz
Kontek, Renata
author_sort Kciuk, Mateusz
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9180621
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91806212022-06-10 Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies Kciuk, Mateusz Mujwar, Somdutt Szymanowska, Anna Marciniak, Beata Bukowski, Karol Mojzych, Mariusz Kontek, Renata Int J Mol Sci Article 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. MDPI 2022-05-24 /pmc/articles/PMC9180621/ /pubmed/35682571 http://dx.doi.org/10.3390/ijms23115892 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kciuk, Mateusz
Mujwar, Somdutt
Szymanowska, Anna
Marciniak, Beata
Bukowski, Karol
Mojzych, Mariusz
Kontek, Renata
Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title_full Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title_fullStr Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title_full_unstemmed Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title_short Preparation of Novel Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides and Their Experimental and Computational Biological Studies
title_sort preparation of novel pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides and their experimental and computational biological studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180621/
https://www.ncbi.nlm.nih.gov/pubmed/35682571
http://dx.doi.org/10.3390/ijms23115892
work_keys_str_mv AT kciukmateusz preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT mujwarsomdutt preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT szymanowskaanna preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT marciniakbeata preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT bukowskikarol preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT mojzychmariusz preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies
AT kontekrenata preparationofnovelpyrazolo43etetrazolo15b124triazinesulfonamidesandtheirexperimentalandcomputationalbiologicalstudies

Ejemplares similares