Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors
A novel series of tri-aryl imidazole derivatives <b>5a</b>–<b>n</b> carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA <b>IX</b> and <b>XII</b> activity. Six compounds were found to be potent and selective...
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/4718 |
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doaj-5fdf0332f65840ef9b6f48807afb78d32021-08-26T14:06:50ZengMDPI AGMolecules1420-30492021-08-01264718471810.3390/molecules26164718Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII InhibitorsLamya H. Al-Wahaibi0Bahaa G. M. Youssif1Ehab S. Taher2Ahmed H. Abdelazeem3Antar A. Abdelhamid4Adel A. Marzouk5Department of Chemistry, College of Sciences, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11564, Saudi ArabiaPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptDepartment of Chemistry, Faculty of Science, Sohag University, Sohag 82524, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, EgyptA novel series of tri-aryl imidazole derivatives <b>5a</b>–<b>n</b> carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA <b>IX</b> and <b>XII</b> activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of <b>5g</b> > <b>5b</b> > <b>5d</b> > <b>5e</b> > <b>5g</b> > <b>5n</b> (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds <b>5g</b> and <b>5b</b> demonstrated higher antiproliferative activity than other tested compounds (with GI<sub>50</sub> = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI<sub>50</sub> = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand <b>9FK</b>. Molecular modelling simulation showed good agreement with the acquired biological evaluation.https://www.mdpi.com/1420-3049/26/16/4718imidazolebenzene sulfonamidecarbonic anhydrase IXXII |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Lamya H. Al-Wahaibi Bahaa G. M. Youssif Ehab S. Taher Ahmed H. Abdelazeem Antar A. Abdelhamid Adel A. Marzouk |
| spellingShingle |
Lamya H. Al-Wahaibi Bahaa G. M. Youssif Ehab S. Taher Ahmed H. Abdelazeem Antar A. Abdelhamid Adel A. Marzouk Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors Molecules imidazole benzene sulfonamide carbonic anhydrase IX XII |
| author_facet |
Lamya H. Al-Wahaibi Bahaa G. M. Youssif Ehab S. Taher Ahmed H. Abdelazeem Antar A. Abdelhamid Adel A. Marzouk |
| author_sort |
Lamya H. Al-Wahaibi |
| title |
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors |
| title_short |
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors |
| title_full |
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors |
| title_fullStr |
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors |
| title_full_unstemmed |
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors |
| title_sort |
design, synthesis, biological evaluation, and computational studies of novel tri-aryl imidazole-benzene sulfonamide hybrids as promising selective carbonic anhydrase ix and xii inhibitors |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2021-08-01 |
| description |
A novel series of tri-aryl imidazole derivatives <b>5a</b>–<b>n</b> carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA <b>IX</b> and <b>XII</b> activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of <b>5g</b> > <b>5b</b> > <b>5d</b> > <b>5e</b> > <b>5g</b> > <b>5n</b> (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds <b>5g</b> and <b>5b</b> demonstrated higher antiproliferative activity than other tested compounds (with GI<sub>50</sub> = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI<sub>50</sub> = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand <b>9FK</b>. Molecular modelling simulation showed good agreement with the acquired biological evaluation. |
| topic |
imidazole benzene sulfonamide carbonic anhydrase IX XII |
| url |
https://www.mdpi.com/1420-3049/26/16/4718 |
| work_keys_str_mv |
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| _version_ |
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