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Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity

[Image: see text] The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative (9), and most of the newly s...

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Autores principales: Turanlı, Sümeyye, Nalbat, Esra, Lengerli, Deniz, İbiş, Kübra, Güntekin Ergün, Sezen, Akhan Güzelcan, Ece, Muyan, Mesut, Cetin-Atalay, Rengul, Çalışkan, Burcu, Banoglu, Erden
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583322/
https://www.ncbi.nlm.nih.gov/pubmed/36278052
http://dx.doi.org/10.1021/acsomega.2c03405
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author Turanlı, Sümeyye
Nalbat, Esra
Lengerli, Deniz
İbiş, Kübra
Güntekin Ergün, Sezen
Akhan Güzelcan, Ece
Muyan, Mesut
Cetin-Atalay, Rengul
Çalışkan, Burcu
Banoglu, Erden
author_facet Turanlı, Sümeyye
Nalbat, Esra
Lengerli, Deniz
İbiş, Kübra
Güntekin Ergün, Sezen
Akhan Güzelcan, Ece
Muyan, Mesut
Cetin-Atalay, Rengul
Çalışkan, Burcu
Banoglu, Erden
author_sort Turanlı, Sümeyye
collection PubMed
description [Image: see text] The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative (9), and most of the newly synthesized derivatives demonstrated moderate to good antiproliferative activities against a panel of hepatocellular carcinoma and breast cancer cells, exemplified with the diaryl isoxazole 11 and the diaryl pyrazole 85 with IC(50) values in the range of 0.7–9.5 μM. Treatments with both 11 and 85 induced apoptosis in these tumor cells, and they displayed antitumor activity in vivo in the Mahlavu hepatocellular carcinoma and the MDA-MB-231 breast cancer xenograft models, indicating that these compounds could be considered as leads for further development of antitumor agents. Important structural features of this compound class for the antitumor activity have also been proposed, which warrant further exploration to guide the design of new and more potent diaryl heterocycles.
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spelling pubmed-95833222022-10-21 Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity Turanlı, Sümeyye Nalbat, Esra Lengerli, Deniz İbiş, Kübra Güntekin Ergün, Sezen Akhan Güzelcan, Ece Muyan, Mesut Cetin-Atalay, Rengul Çalışkan, Burcu Banoglu, Erden ACS Omega [Image: see text] The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative (9), and most of the newly synthesized derivatives demonstrated moderate to good antiproliferative activities against a panel of hepatocellular carcinoma and breast cancer cells, exemplified with the diaryl isoxazole 11 and the diaryl pyrazole 85 with IC(50) values in the range of 0.7–9.5 μM. Treatments with both 11 and 85 induced apoptosis in these tumor cells, and they displayed antitumor activity in vivo in the Mahlavu hepatocellular carcinoma and the MDA-MB-231 breast cancer xenograft models, indicating that these compounds could be considered as leads for further development of antitumor agents. Important structural features of this compound class for the antitumor activity have also been proposed, which warrant further exploration to guide the design of new and more potent diaryl heterocycles. American Chemical Society 2022-10-03 /pmc/articles/PMC9583322/ /pubmed/36278052 http://dx.doi.org/10.1021/acsomega.2c03405 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Turanlı, Sümeyye
Nalbat, Esra
Lengerli, Deniz
İbiş, Kübra
Güntekin Ergün, Sezen
Akhan Güzelcan, Ece
Muyan, Mesut
Cetin-Atalay, Rengul
Çalışkan, Burcu
Banoglu, Erden
Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title_full Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title_fullStr Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title_full_unstemmed Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title_short Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity
title_sort vicinal diaryl-substituted isoxazole and pyrazole derivatives with in vitro growth inhibitory and in vivo antitumor activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583322/
https://www.ncbi.nlm.nih.gov/pubmed/36278052
http://dx.doi.org/10.1021/acsomega.2c03405
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