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Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel ch...

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Autores principales: Darwish, Mahmoud I. M., Moustafa, Ahmed M., Youssef, Asmaa M., Mansour, Mohamed, Yousef, Ahmed I., El Omri, Abdelfatteh, Shawki, Hossam H., Mohamed, Magda F., Hassaneen, Hamdi M., Abdelhamid, Ismail A., Oishi, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144155/
https://www.ncbi.nlm.nih.gov/pubmed/37110575
http://dx.doi.org/10.3390/molecules28083338
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author Darwish, Mahmoud I. M.
Moustafa, Ahmed M.
Youssef, Asmaa M.
Mansour, Mohamed
Yousef, Ahmed I.
El Omri, Abdelfatteh
Shawki, Hossam H.
Mohamed, Magda F.
Hassaneen, Hamdi M.
Abdelhamid, Ismail A.
Oishi, Hisashi
author_facet Darwish, Mahmoud I. M.
Moustafa, Ahmed M.
Youssef, Asmaa M.
Mansour, Mohamed
Yousef, Ahmed I.
El Omri, Abdelfatteh
Shawki, Hossam H.
Mohamed, Magda F.
Hassaneen, Hamdi M.
Abdelhamid, Ismail A.
Oishi, Hisashi
author_sort Darwish, Mahmoud I. M.
collection PubMed
description Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer.
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spelling pubmed-101441552023-04-29 Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis Darwish, Mahmoud I. M. Moustafa, Ahmed M. Youssef, Asmaa M. Mansour, Mohamed Yousef, Ahmed I. El Omri, Abdelfatteh Shawki, Hossam H. Mohamed, Magda F. Hassaneen, Hamdi M. Abdelhamid, Ismail A. Oishi, Hisashi Molecules Article Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer. MDPI 2023-04-10 /pmc/articles/PMC10144155/ /pubmed/37110575 http://dx.doi.org/10.3390/molecules28083338 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Darwish, Mahmoud I. M.
Moustafa, Ahmed M.
Youssef, Asmaa M.
Mansour, Mohamed
Yousef, Ahmed I.
El Omri, Abdelfatteh
Shawki, Hossam H.
Mohamed, Magda F.
Hassaneen, Hamdi M.
Abdelhamid, Ismail A.
Oishi, Hisashi
Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title_full Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title_fullStr Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title_full_unstemmed Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title_short Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis
title_sort novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcones suppress breast carcinoma through cell cycle arrests and apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144155/
https://www.ncbi.nlm.nih.gov/pubmed/37110575
http://dx.doi.org/10.3390/molecules28083338
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