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New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity
A novel series of 1,2,3-triazole/1,2,4-triazole hybrids 5a, 5b, and 6a–i was designed and synthesized as antiproliferative agents targeting aromatase enzymes. The antiproliferative activity of the new hybrids against four cancer cells was studied using Erlotinib as a control. Compounds 6a and 6b dem...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609154/ https://www.ncbi.nlm.nih.gov/pubmed/37894571 http://dx.doi.org/10.3390/molecules28207092 |
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author | Maghraby, Mohamed T-E Mazyad Almutairi, Tahani Bräse, Stefan Salem, Ola I. A. Youssif, Bahaa G. M. Sheha, Mahmoud M. |
author_facet | Maghraby, Mohamed T-E Mazyad Almutairi, Tahani Bräse, Stefan Salem, Ola I. A. Youssif, Bahaa G. M. Sheha, Mahmoud M. |
author_sort | Maghraby, Mohamed T-E |
collection | PubMed |
description | A novel series of 1,2,3-triazole/1,2,4-triazole hybrids 5a, 5b, and 6a–i was designed and synthesized as antiproliferative agents targeting aromatase enzymes. The antiproliferative activity of the new hybrids against four cancer cells was studied using Erlotinib as a control. Compounds 6a and 6b demonstrated the highest antiproliferative activity among these hybrids, with GI50 values of 40 nM and 35 nM, respectively. Compound 6b was the most potent derivative, with a GI50 of 35 nM, comparable to Erlotinib’s GI50 of 33 nM. Compound 6b inhibited all cancer cell lines with comparable efficacy to Erlotinib. Compounds 5a, 5b, and 6a–i were tested for inhibitory action against aromatase as a potential target for their antiproliferative activity. Results revealed that compounds 6a and 6b were the most potent aromatase inhibitors, with IC50 values of 0.12 ± 0.01 µM and 0.09 ± 0.01 µM, respectively, being more potent than the reference Ketoconazole (IC50 = 2.6 ± 0.20 µM) but less potent than Letrozole (IC50 = 0.002 ± 0.0002). These findings indicated that compounds 6a and 6b had significant aromatase inhibitory action and are potential antiproliferative candidates. The findings were further linked to molecular docking investigations, which gave models of strong interactions with the aromatase domain for inhibitors with high binding scores. |
format | Online Article Text |
id | pubmed-10609154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106091542023-10-28 New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity Maghraby, Mohamed T-E Mazyad Almutairi, Tahani Bräse, Stefan Salem, Ola I. A. Youssif, Bahaa G. M. Sheha, Mahmoud M. Molecules Article A novel series of 1,2,3-triazole/1,2,4-triazole hybrids 5a, 5b, and 6a–i was designed and synthesized as antiproliferative agents targeting aromatase enzymes. The antiproliferative activity of the new hybrids against four cancer cells was studied using Erlotinib as a control. Compounds 6a and 6b demonstrated the highest antiproliferative activity among these hybrids, with GI50 values of 40 nM and 35 nM, respectively. Compound 6b was the most potent derivative, with a GI50 of 35 nM, comparable to Erlotinib’s GI50 of 33 nM. Compound 6b inhibited all cancer cell lines with comparable efficacy to Erlotinib. Compounds 5a, 5b, and 6a–i were tested for inhibitory action against aromatase as a potential target for their antiproliferative activity. Results revealed that compounds 6a and 6b were the most potent aromatase inhibitors, with IC50 values of 0.12 ± 0.01 µM and 0.09 ± 0.01 µM, respectively, being more potent than the reference Ketoconazole (IC50 = 2.6 ± 0.20 µM) but less potent than Letrozole (IC50 = 0.002 ± 0.0002). These findings indicated that compounds 6a and 6b had significant aromatase inhibitory action and are potential antiproliferative candidates. The findings were further linked to molecular docking investigations, which gave models of strong interactions with the aromatase domain for inhibitors with high binding scores. MDPI 2023-10-14 /pmc/articles/PMC10609154/ /pubmed/37894571 http://dx.doi.org/10.3390/molecules28207092 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 Maghraby, Mohamed T-E Mazyad Almutairi, Tahani Bräse, Stefan Salem, Ola I. A. Youssif, Bahaa G. M. Sheha, Mahmoud M. New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title | New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title_full | New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title_fullStr | New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title_full_unstemmed | New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title_short | New 1,2,3-Triazole/1,2,4-triazole Hybrids as Aromatase Inhibitors: Design, Synthesis, and Apoptotic Antiproliferative Activity |
title_sort | new 1,2,3-triazole/1,2,4-triazole hybrids as aromatase inhibitors: design, synthesis, and apoptotic antiproliferative activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609154/ https://www.ncbi.nlm.nih.gov/pubmed/37894571 http://dx.doi.org/10.3390/molecules28207092 |
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