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Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9
Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole deriv...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152322/ https://www.ncbi.nlm.nih.gov/pubmed/28677624 http://dx.doi.org/10.3390/molecules22071109 |
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author | Özdemir, Ahmet Sever, Belgin Altıntop, Mehlika Dilek Temel, Halide Edip Atlı, Özlem Baysal, Merve Demirci, Fatih |
author_facet | Özdemir, Ahmet Sever, Belgin Altıntop, Mehlika Dilek Temel, Halide Edip Atlı, Özlem Baysal, Merve Demirci, Fatih |
author_sort | Özdemir, Ahmet |
collection | PubMed |
description | Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for their anticancer effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. In order to examine the relationship between their anticancer activity and MMP-9, the compounds were evaluated for their inhibitory effects on MMPs. N-(1,3-Benzodioxol-5-ylmethyl)-2-{[5-(((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)-1,3,4-oxadiazol-2-yl]thio}acetamide (8) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide (9) revealed promising cytotoxic effects on A549 and C6 cell lines similar to cisplatin without causing any toxicity towards NIH/3T3 mouse embryonic fibroblast cell line. Compounds 8 and 9 were also the most effective MMP-9 inhibitors in this series. Moreover, docking studies pointed out that compounds 8 and 9 had good affinity to the active site of the MMP-9 enzyme. The molecular docking and in vitro studies suggest that the MMP-9 inhibitory effects of compounds 8 and 9 may play an important role in lung adenocarcinoma and glioma treatment. |
format | Online Article Text |
id | pubmed-6152322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61523222018-11-13 Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 Özdemir, Ahmet Sever, Belgin Altıntop, Mehlika Dilek Temel, Halide Edip Atlı, Özlem Baysal, Merve Demirci, Fatih Molecules Article Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for their anticancer effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. In order to examine the relationship between their anticancer activity and MMP-9, the compounds were evaluated for their inhibitory effects on MMPs. N-(1,3-Benzodioxol-5-ylmethyl)-2-{[5-(((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)-1,3,4-oxadiazol-2-yl]thio}acetamide (8) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide (9) revealed promising cytotoxic effects on A549 and C6 cell lines similar to cisplatin without causing any toxicity towards NIH/3T3 mouse embryonic fibroblast cell line. Compounds 8 and 9 were also the most effective MMP-9 inhibitors in this series. Moreover, docking studies pointed out that compounds 8 and 9 had good affinity to the active site of the MMP-9 enzyme. The molecular docking and in vitro studies suggest that the MMP-9 inhibitory effects of compounds 8 and 9 may play an important role in lung adenocarcinoma and glioma treatment. MDPI 2017-07-04 /pmc/articles/PMC6152322/ /pubmed/28677624 http://dx.doi.org/10.3390/molecules22071109 Text en © 2017 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 Özdemir, Ahmet Sever, Belgin Altıntop, Mehlika Dilek Temel, Halide Edip Atlı, Özlem Baysal, Merve Demirci, Fatih Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title | Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title_full | Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title_fullStr | Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title_full_unstemmed | Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title_short | Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9 |
title_sort | synthesis and evaluation of new oxadiazole, thiadiazole, and triazole derivatives as potential anticancer agents targeting mmp-9 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152322/ https://www.ncbi.nlm.nih.gov/pubmed/28677624 http://dx.doi.org/10.3390/molecules22071109 |
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