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The activity of pyrazolo4,3- e 1,2,4triazine and pyrazolo4,3- e tetrazolo1,5- b 1,2,4triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures
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The activity of pyrazolo4,3- e 1,2,4triazine and pyrazolo4,3- e tetrazolo1,5- b 1,2,4triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures
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Journal Article
The activity of pyrazolo4,3- e 1,2,4triazine and pyrazolo4,3- e tetrazolo1,5- b 1,2,4triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures
2024
Overview
In the last decade, an increasing interest in compounds containing pyrazolo[4,3-
][1,2,4]triazine moiety is observed. Therefore, the aim of the research was to synthesise a novel sulphonyl pyrazolo[4,3-
][1,2,4]triazines (
,
) and pyrazolo[4,3-
]tetrazolo[1,5-
][1,2,4]triazine sulphonamide derivatives (
,
) to assess their anticancer activity. The MTT assay showed that
,
,
,
have stronger cytotoxic activity than cisplatin in both breast cancer cells (MCF-7 and MDA-MB-231) and exhibited weaker effect on normal breast cells (MCF-10A). The obtained results showed that the most active compound
increased apoptosis via caspase 9, caspase 8, and caspase 3/7. It is worth to note that compound
suppressed NF-κB expression and promoted p53, Bax, and ROS which play important role in activation of apoptosis. Moreover, our results confirmed that compound
triggers autophagy through increased formation of autophagosomes, expression of beclin-1 and mTOR inhibition. Thus, our study defines a possible mechanism underlying
-induced anti-cancer activity against breast cancer cell lines.
Publisher
Taylor & Francis Ltd,Taylor & Francis,Taylor & Francis Group
Subject
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cell Proliferation - drug effects
/ Dose-Response Relationship, Drug
/ Drug Screening Assays, Antitumor
/ Female
/ Humans
/ Pyrazoles - chemical synthesis
/ pyrazolo[43-e][1,2,4]triazine
/ Pyrazolo[43-e]tetrazolo[15-b][1,2,4]triazine
/ spheroid
/ Spheroids, Cellular - drug effects
/ Structure-Activity Relationship
/ Sulfonamides - chemical synthesis
/ Triazine
