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In vitro characterization of arylhydrazones of active methylene derivatives
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, externali...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856940/ https://www.ncbi.nlm.nih.gov/pubmed/29556135 http://dx.doi.org/10.1016/j.jsps.2017.12.018 |
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author | Palanivel, Suresh Zhurina, Anastasia Doan, Phuong Chandraseelan, Jerome G. Khandelwal, Vinoth Kumar Megraj Zubkov, Fedor I. Mahmudov, Kamran T. Pombeiro, Armando J.L. Yli-Harja, Olli Kandhavelu, Meenakshisundaram |
author_facet | Palanivel, Suresh Zhurina, Anastasia Doan, Phuong Chandraseelan, Jerome G. Khandelwal, Vinoth Kumar Megraj Zubkov, Fedor I. Mahmudov, Kamran T. Pombeiro, Armando J.L. Yli-Harja, Olli Kandhavelu, Meenakshisundaram |
author_sort | Palanivel, Suresh |
collection | PubMed |
description | 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, 5-(2-(2-hydroxyphenyl) hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (5), 4-hydroxy-5-(2-(2,4,6-trioxo-tetrahydro-pyrimidin-5(6H) ylidene)hydrazinyl)benzene-1,3-disulfonic acid (6), 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxybenzenesulfonic acid (8), 5-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-4-hydroxybenzene-1,3-disulfonic acid (9) and 2-(2-sulfophenylhydrazo)malononitrile (10) were chosen for the pharmacodynamics study. Among these, compound 5 exhibited the better cytotoxic effect with the IC(50) 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 Ca(2+) up-regulation in compound treated cells. A brief inspection of the effect of the compound 5 against multiple human brain astrocytoma cells showed a better cell growth inhibitory effect at micro molar level. These systematic studies provide insights in the development of novel AHAMACs compounds as potential cell growth inhibitors for cancer treatment. |
format | Online Article Text |
id | pubmed-5856940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-58569402018-03-19 In vitro characterization of arylhydrazones of active methylene derivatives Palanivel, Suresh Zhurina, Anastasia Doan, Phuong Chandraseelan, Jerome G. Khandelwal, Vinoth Kumar Megraj Zubkov, Fedor I. Mahmudov, Kamran T. Pombeiro, Armando J.L. Yli-Harja, Olli Kandhavelu, Meenakshisundaram Saudi Pharm J Article 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, 5-(2-(2-hydroxyphenyl) hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (5), 4-hydroxy-5-(2-(2,4,6-trioxo-tetrahydro-pyrimidin-5(6H) ylidene)hydrazinyl)benzene-1,3-disulfonic acid (6), 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxybenzenesulfonic acid (8), 5-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-4-hydroxybenzene-1,3-disulfonic acid (9) and 2-(2-sulfophenylhydrazo)malononitrile (10) were chosen for the pharmacodynamics study. Among these, compound 5 exhibited the better cytotoxic effect with the IC(50) 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 Ca(2+) up-regulation in compound treated cells. A brief inspection of the effect of the compound 5 against multiple human brain astrocytoma cells showed a better cell growth inhibitory effect at micro molar level. These systematic studies provide insights in the development of novel AHAMACs compounds as potential cell growth inhibitors for cancer treatment. Elsevier 2018-03 2018-01-02 /pmc/articles/PMC5856940/ /pubmed/29556135 http://dx.doi.org/10.1016/j.jsps.2017.12.018 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Palanivel, Suresh Zhurina, Anastasia Doan, Phuong Chandraseelan, Jerome G. Khandelwal, Vinoth Kumar Megraj Zubkov, Fedor I. Mahmudov, Kamran T. Pombeiro, Armando J.L. Yli-Harja, Olli Kandhavelu, Meenakshisundaram In vitro characterization of arylhydrazones of active methylene derivatives |
title | In vitro characterization of arylhydrazones of active methylene derivatives |
title_full | In vitro characterization of arylhydrazones of active methylene derivatives |
title_fullStr | In vitro characterization of arylhydrazones of active methylene derivatives |
title_full_unstemmed | In vitro characterization of arylhydrazones of active methylene derivatives |
title_short | In vitro characterization of arylhydrazones of active methylene derivatives |
title_sort | in vitro characterization of arylhydrazones of active methylene derivatives |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856940/ https://www.ncbi.nlm.nih.gov/pubmed/29556135 http://dx.doi.org/10.1016/j.jsps.2017.12.018 |
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