Analysis of the Antitumor Activity of Four New Phenylpyrazolotriazine Derivatives In Vitro in a Cytotoxicity and Cytostatic Study on Breast Cancer Cell Cultures
https://doi.org/10.37489/0235-2990-202570-7-8-19-27
EDN: XNQQIZ
Abstract
Background. The work presents the results of a study of new phenylpyrazolotriazine derivatives in order to establish their potential use as anticancer agents, including for chemotherapy of metastatic breast cancer. The relevance of the work is due to the widespread prevalence of oncological diseases and high breast cancer mortality, which dictate the need for the continuous development of new antitumor drugs.
The aim of the study. Screening of the antitumor potential of four new phenylpyrazolotriazine derivatives by testing their cytotoxic (CTA) and cytostatic (CSA) activity on breast cancer cell cultures.
Materials and methods. The base methods used in this study are the culturing of MCF-7, MDAMB231, BT474, and MCF-10a cells, as well as determining the CTA and CSA activity of four new phenylpyrazolotriazine derivatives at concentrations from 0.25 to 10.0 mM/L.
Results. For the MCF-7 culture, the maximum cell viability inhibition of the comparison drug temozolomide was equal to 2.44 and the concentration causing 50% cell death (IC₅₀) was 6.81 mM/L; for other cultures, CTA indicators were lower. Phenylpyrazolotriazine 3 demonstrated lower activity compared to temozolomide, IC₅₀ was not achieved in most cases. This derivative has been classified as a compound with low CTA and moderate CSA. Phenylpyrazolotriazines 1 and 4 showed higher activity than the comparison drug and were classified as compounds with low or moderate CTA and moderate CSA. Finally, phenylpyrazolotriazine 2 with a maximum cell viability inhibition of 3.70 and IC₅₀ of 1.66 mM/L showed the highest values of CTA and CSA.
Conclusion. According to the results of the in vitro study, four new phenylpyrazolotriazine derivatives can be evaluated in ascending order of the CTA and CSA combination: phenylpyrazolotriazine 3 ˂ temozolomide ˂ phenylpyrazolotriazines 1 and 4 ˂ phenylpyrazolotriazine 2. Thus, 3-(3'-Phenyl-4'methoxycarbonyl-isoxazolyl)-7-(p-tolyl)-pyrazolo[5,1-c][1,2,4]triazine (phenylpyrazolotriazine 2) is the undisputed leader in the tested series of new imidazotriazine derivatives and is recommended for further preclinical trials.
Keywords
phenylpyrazolotriazine,
cytotoxic activity,
cytostatic activity,
breast cancer,
MCF-7 cell line,
MDAMB231 cell line,
BT474 cell line,
MCF-10a cell line
Supporting agencies: The authors express their gratitude to Corresponding Member of the Russian Academy of Sciences, Prof. V. V. Udut (Head of the Laboratory of Physiology, Molecular and Clinical Pharmacology, Deputy Director for Scientific and Therapeutic Work of the E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine of the Tomsk National Research Medical Center of the Russian Academy of Sciences) for useful discussions; the authors are also grateful to Corresponding Member of the Russian Academy of Sciences, Prof. N. V. Cherdyntseva (Head of the Laboratory of Molecular Oncology and Cancer Immunology, Deputy Director for Scientific Work of the Research Institute of Oncology of the Tomsk National Research Medical Center of the Russian Academy of Sciences) for provided cell lines and materials and their structuring for subsequent analysis. The authors declare a lack of funding
About the Authors
Ah. H. Al-Humairi
Volgograd State Medical University; National Research Tomsk State University
Russian Federation
Competing Interests:
Russian Federation
Ahmed H. Al-Humairi — Lecturer at the Department of Disaster Medicine, Institute of Public Health, VSMU; National Research Tomsk State University of the Ministry of Science and Higher Education of the RF.
Volgograd
Competing Interests:
The authors have no conflict of interest to declare
V. V. Novochadov
Volgograd State University
Russian Federation
Competing Interests:
Russian Federation
Valeriy V. Novochadov — D. Sc. in Medicine, Professor at the Department of Biology and Bioengineering, Institute of Natural Sciences.
Volgograd
Competing Interests:
The authors have no conflict of interest to declare
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For citations:
Al-Humairi AH, Novochadov VV. Analysis of the Antitumor Activity of Four New Phenylpyrazolotriazine Derivatives In Vitro in a Cytotoxicity and Cytostatic Study on Breast Cancer Cell Cultures. Antibiotiki i Khimioterapiya = Antibiotics and Chemotherapy. 2025;70(7-8):19-27. (In Russ.) https://doi.org/10.37489/0235-2990-202570-7-8-19-27. EDN: XNQQIZ
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