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Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the comp...

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Autores principales: Altıntop, Mehlika Dilek, Temel, Halide Edip, Sever, Belgin, Akalın Çiftçi, Gülşen, Kaplancıklı, Zafer Asım
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273715/
https://www.ncbi.nlm.nih.gov/pubmed/27879683
http://dx.doi.org/10.3390/molecules21111598
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author Altıntop, Mehlika Dilek
Temel, Halide Edip
Sever, Belgin
Akalın Çiftçi, Gülşen
Kaplancıklı, Zafer Asım
author_facet Altıntop, Mehlika Dilek
Temel, Halide Edip
Sever, Belgin
Akalın Çiftçi, Gülşen
Kaplancıklı, Zafer Asım
author_sort Altıntop, Mehlika Dilek
collection PubMed
description New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1′-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases.
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spelling pubmed-62737152018-12-28 Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents Altıntop, Mehlika Dilek Temel, Halide Edip Sever, Belgin Akalın Çiftçi, Gülşen Kaplancıklı, Zafer Asım Molecules Article New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1′-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases. MDPI 2016-11-22 /pmc/articles/PMC6273715/ /pubmed/27879683 http://dx.doi.org/10.3390/molecules21111598 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Altıntop, Mehlika Dilek
Temel, Halide Edip
Sever, Belgin
Akalın Çiftçi, Gülşen
Kaplancıklı, Zafer Asım
Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title_full Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title_fullStr Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title_full_unstemmed Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title_short Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents
title_sort synthesis and evaluation of new benzodioxole- based thiosemicarbazone derivatives as potential antitumor agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273715/
https://www.ncbi.nlm.nih.gov/pubmed/27879683
http://dx.doi.org/10.3390/molecules21111598
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