| Autor: |
Maghraby MT; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt., Mazyad Almutairi T; Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Bräse S; Institute of Biological and Chemical Systems, IBCS-FMS, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany., Salem OIA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt., Youssif BGM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt., Sheha MM; Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, New-Assiut 71684, Egypt. |
| Abstrakt: |
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. |
