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Toxicity assessment of arylhydrazones of active methylene compoundsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Palanivel Suresh, Chandraseelan Jerome G., Yli-Harja Olli, Kandhavelu Meenakshisundaram, Guseinov Firudin I., Zubkov Fedor I., Mahmudov Kamran T., Pombeiro Armando J.L.
- Журнал: Journal of Hazardous Materials
- Год издания: 2016
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Аннотация: Arylhydrazones of active methylene compounds (AHAMCs) are potent chemotherapy agents for the cancer treatment. AHAMCs enhance the apoptotic cell death and antiproliferation properties in cancer cells. In this study, a series of AHAMCs, 13 compounds, was assayed for cytotoxicity, apoptosis, externalization of phosphatidylserine, heterogeneity and cellular calcium level changes. The in vitro cytotoxicity study against HEK293T cells suggests that AHAMCs have significant cytotoxic effect over the concentrations. Top 5 compounds (Z)-5-chloro-2-hydroxy-3-(2-(4,4,4-trifluoro-1,3-dioxo-1-(thiophen-2-yl)butan-2-ylidene)hydrazinyl)benzenesulfonic acid (5), 5-(2-(4,4-dimethyl-2,6-dioxocyclo-hexylidene)hydrazinyl)-4-hydroxybenzene-1,3-disulfonic acid (6), 5-chloro-2-hydroxy-3-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazinyl) benzenesulfonic acid (8), 5-(2-(2-hydroxy-4-nitrophenyl)hydrazono)pyrimidine-2,4,6 (1H,3H,5H)-trione (9) and 4-hydroxy-5-(2-(2,4,6-trioxotetra-hydropyrimidin-5(2H)-ylidene) hydrazinyl)benzene-1,3-disulfonic acid (10) were chosen for the pharmacodynamics study. Among these, compound 5 exhibited the better cytotoxic effect with the IC50 of 50.86±2.5 mM. DNA cleavage study revealed that 5 induces cell death through apoptosis and shows more effects after 24 and/or 48 h. Independent validation of apoptosis by following the externalization of phosphatidylserine using Annexin-V is also in agreement with the potential activity of 5. Single cell image analysis of Annexin-V bound cells confirms the presence of mixture of early, mid and late apoptotic cells in the population of the cells treated with 5 and a decreased trend in cell-to-cell variation over the phase was also identified. Additionally, intracellular calcium level measurements identified the Ca2+ up-regulation in compound treated cells. Overall, the study suggests that compound 5 is the potential cytotoxic compound that induce more apoptosis in immortal cells and can be used to treat different types of cancer.
- Добавил в систему: Гусейнов Фирудин Ильясович