Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer

被引：27

作者：

Hermanowicz, Justyna Magdalena ^{[1
,2
]}

Szymanowska, Anna ^{[3
]}

Sieklucka, Beata ^{[1
]}

Czarnomysy, Robert ^{[4
]}

Pawlak, Krystyna ^{[5
]}

Bielawska, Anna ^{[3
,4
]}

Bielawski, Krzysztof ^{[4
]}

Kalafut, Joanna ^{[6
]}

Przybyszewska, Alicja ^{[6
]}

Surazynski, Arkadiusz ^{[7
]}

Rivero-Muller, Adolfo ^{[6
]}

Mojzych, Mariusz ^{[8
]}

Pawlak, Dariusz ^{[1
,9
]}

机构：

[1] Med Univ Bialystok, Dept Pharmacodynam, Mickiewicza 2C, PL-15222 Bialystok, Poland

[2] Med Univ Bialystok, Dept Clin Pharm, Bialystok, Poland

[3] Med Univ Bialystok, Dept Biotechnol, Bialystok, Poland

[4] Med Univ Bialystok, Dept Synth & Technol Drugs, Bialystok, Poland

[5] Med Univ Bialystok, Dept Monitored Pharmacotherapy, Bialystok, Poland

[6] Med Univ Lublin, Dept Biochem & Mol Biol, Lublin, Poland

[7] Med Univ Bialystok, Dept Med Chem, Bialystok, Poland

[8] Siedlce Univ Nat Sci & Humanities, Dept Chem, Siedlce, Poland

[9] Univ Warmia & Mazury, Fac Med, Dept Pharmacol & Toxicol, Olsztyn, Poland

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2021年 / 36卷 / 01期

关键词：

1,2,4-Triazine derivative; apoptosis; colon cancer; zebrafish; DEPENDENT KINASE INHIBITOR; BRUTONS TYROSINE KINASE; IN-VITRO; CYTOTOXIC ACTIVITY; ROSCOVITINE; ZEBRAFISH; APOPTOSIS; LFM-A13; CELLS; ERYTHROPOIETIN;

D O I：

10.1080/14756366.2021.1879803

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.

引用

页码：535 / 548

页数：14

共 52 条

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