Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice
Breast cancer (BC) is one of the most common types of malignant tumors, which makes scientific research in this area extremely relevant. The difficulties of breast cancer chemotherapy stimulate the search for new drugs to treat this nosology. Derivatives of imidazotriazine and imidazotetrazine, whic...
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Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2024-01-01
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| Series: | Фармация и фармакология (Пятигорск) |
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| Online Access: | https://www.pharmpharm.ru/jour/article/view/1382 |
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| author | A. H. Al-Humairi D. L. Speransky V. V. Novochadov S. V. Poroisky N. V. Cherdyntseva V. V. Udut |
| author_facet | A. H. Al-Humairi D. L. Speransky V. V. Novochadov S. V. Poroisky N. V. Cherdyntseva V. V. Udut |
| author_sort | A. H. Al-Humairi |
| collection | DOAJ |
| description | Breast cancer (BC) is one of the most common types of malignant tumors, which makes scientific research in this area extremely relevant. The difficulties of breast cancer chemotherapy stimulate the search for new drugs to treat this nosology. Derivatives of imidazotriazine and imidazotetrazine, which are analogues of the antitumor drug temozolamide, can be ones of the promising drugs in this regard.The aim of the work was to evaluate the antitumor activity of three new azoloazine derivatives in a xenogeneic breast cancer model in mice in vivo.Materials and methods. A study was conducted on a xenogeneic model of BC. After the immunosuppression with azathioprine, 48 white BALB/c mice were injected with MCF-7 cells, test derivatives, and the reference drug epirubicin at doses of 1/2 IC50 and 1/10 IC50, into the base of the mammary gland once. The body weight of the mice was monitored; on the 15th day, at the end of the experiment, the relative volume was assessed.Results and discussion. Among the three compounds studied, imidazotetrazine 1 showed the most encouraging results: stopping the loss of body weight in the mice caused by the administration of tumor cells, and reducing the tumor volume on the 15th day of the experiment to 50.6% of that in the control when using a dose of 1/10 IC50, up to 39.2% – when using a dose of 1/2 IC50, which significantly exceeded the values of the reference drug epirubicin and the values in the control group. In the histological examination, the signs of spread and preservation of tumor cells viability of the MCF-7 line after its administration were minimal, the value of the histological malignancy index decreased by 9.3% of the control value.Conclusion. Among the tested azoloazine derivatives, 3-cyclohexyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-N-piperidinylcarboxamide is the undisputed leader, causing inhibition of the tumor growth in a xenogeneic model in vivo. |
| format | Article |
| id | doaj-art-76991f9ba82a42c0bfd83cdce2eaf466 |
| institution | DOAJ |
| issn | 2307-9266 2413-2241 |
| language | Russian |
| publishDate | 2024-01-01 |
| publisher | Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
| record_format | Article |
| series | Фармация и фармакология (Пятигорск) |
| spelling | doaj-art-76991f9ba82a42c0bfd83cdce2eaf4662025-08-20T02:55:58ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412024-01-0111429130010.19163/2307-9266-2023-11-4-291-300488Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into miceA. H. Al-Humairi0D. L. Speransky1V. V. Novochadov2S. V. Poroisky3N. V. Cherdyntseva4V. V. Udut5Volgograd State Medical University. Research institute of Pharmacology and Regenerative Medicine named after E.D. Goldberg, Tomsk National Research Medical Center of the Russian Academy of SciencesVolgograd State Medical UniversityVolgograd State UniversityVolgograd State Medical UniversityResearch Institute of Oncology, Tomsk National Research Medical Center of the Russian Academy of SciencesResearch institute of Pharmacology and Regenerative Medicine named after E.D. Goldberg, Tomsk National Research Medical Center of the Russian Academy of SciencesBreast cancer (BC) is one of the most common types of malignant tumors, which makes scientific research in this area extremely relevant. The difficulties of breast cancer chemotherapy stimulate the search for new drugs to treat this nosology. Derivatives of imidazotriazine and imidazotetrazine, which are analogues of the antitumor drug temozolamide, can be ones of the promising drugs in this regard.The aim of the work was to evaluate the antitumor activity of three new azoloazine derivatives in a xenogeneic breast cancer model in mice in vivo.Materials and methods. A study was conducted on a xenogeneic model of BC. After the immunosuppression with azathioprine, 48 white BALB/c mice were injected with MCF-7 cells, test derivatives, and the reference drug epirubicin at doses of 1/2 IC50 and 1/10 IC50, into the base of the mammary gland once. The body weight of the mice was monitored; on the 15th day, at the end of the experiment, the relative volume was assessed.Results and discussion. Among the three compounds studied, imidazotetrazine 1 showed the most encouraging results: stopping the loss of body weight in the mice caused by the administration of tumor cells, and reducing the tumor volume on the 15th day of the experiment to 50.6% of that in the control when using a dose of 1/10 IC50, up to 39.2% – when using a dose of 1/2 IC50, which significantly exceeded the values of the reference drug epirubicin and the values in the control group. In the histological examination, the signs of spread and preservation of tumor cells viability of the MCF-7 line after its administration were minimal, the value of the histological malignancy index decreased by 9.3% of the control value.Conclusion. Among the tested azoloazine derivatives, 3-cyclohexyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-N-piperidinylcarboxamide is the undisputed leader, causing inhibition of the tumor growth in a xenogeneic model in vivo.https://www.pharmpharm.ru/jour/article/view/1382imidazotriazineimidazotetrazinebreast cancermcf-7 cell linemouse models |
| spellingShingle | A. H. Al-Humairi D. L. Speransky V. V. Novochadov S. V. Poroisky N. V. Cherdyntseva V. V. Udut Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice Фармация и фармакология (Пятигорск) imidazotriazine imidazotetrazine breast cancer mcf-7 cell line mouse models |
| title | Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| title_full | Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| title_fullStr | Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| title_full_unstemmed | Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| title_short | Antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| title_sort | antitumor activity of three new azoloazine derivatives in orthotopic transplantation model of human breast cancer cells into mice |
| topic | imidazotriazine imidazotetrazine breast cancer mcf-7 cell line mouse models |
| url | https://www.pharmpharm.ru/jour/article/view/1382 |
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