Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Maghraby, Mohamed T-E, Mazyad Almutairi, Tahani, Bräse, Stefan, Salem, Ola I. A., Youssif, Bahaa G. M., Sheha, Mahmoud M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785127946749476864
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
work_keys_str_mv AT maghrabymohamedte new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity
AT mazyadalmutairitahani new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity
AT brasestefan new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity
AT salemolaia new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity
AT youssifbahaagm new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity
AT shehamahmoudm new123triazole124triazolehybridsasaromataseinhibitorsdesignsynthesisandapoptoticantiproliferativeactivity