Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors
Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/3/816 |
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| author | Kashif Rafiq Najeeb Ur Rehman Sobia Ahsan Halim Majid Khan Ajmal Khan Ahmed Al-Harrasi |
| author_facet | Kashif Rafiq Najeeb Ur Rehman Sobia Ahsan Halim Majid Khan Ajmal Khan Ahmed Al-Harrasi |
| author_sort | Kashif Rafiq |
| collection | DOAJ |
| description | Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids (<b>4a</b>–<b>l</b>), characterized by <sup>1</sup>H- and <sup>13</sup>C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives <b>4a</b>–<b>l</b> exhibited selective inhibition against CA-II. All the compounds (except <b>4d</b>) exhibited good to moderate CA-II inhibitory activities with IC<sub>50</sub> value in range of 12.1 to 53.6 µM. Among all the compounds, <b>4a</b> (12.1 ± 0.86 µM), <b>4c</b> (13.8 ± 0.64 µM), <b>4b</b> (19.1 ± 0.88 µM) and <b>4h</b> (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II. |
| first_indexed | 2024-03-09T23:29:24Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:29:24Z |
| publishDate | 2022-01-01 |
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| series | Molecules |
| spelling | doaj.art-98d9e98af9634ea98f17b75c2caf6a592023-11-23T17:13:05ZengMDPI AGMolecules1420-30492022-01-0127381610.3390/molecules27030816Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II InhibitorsKashif Rafiq0Najeeb Ur Rehman1Sobia Ahsan Halim2Majid Khan3Ajmal Khan4Ahmed Al-Harrasi5Natural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, P.O Box 33, Birkat Al Mauz, Nizwa 616, OmanCarbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids (<b>4a</b>–<b>l</b>), characterized by <sup>1</sup>H- and <sup>13</sup>C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives <b>4a</b>–<b>l</b> exhibited selective inhibition against CA-II. All the compounds (except <b>4d</b>) exhibited good to moderate CA-II inhibitory activities with IC<sub>50</sub> value in range of 12.1 to 53.6 µM. Among all the compounds, <b>4a</b> (12.1 ± 0.86 µM), <b>4c</b> (13.8 ± 0.64 µM), <b>4b</b> (19.1 ± 0.88 µM) and <b>4h</b> (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II.https://www.mdpi.com/1420-3049/27/3/8163-phenyl-β-alanine 1,3,4-oxadiazole hybridscarbonic anhydrase-IIα-glucosidasestructure-activity relationshipmolecular docking |
| spellingShingle | Kashif Rafiq Najeeb Ur Rehman Sobia Ahsan Halim Majid Khan Ajmal Khan Ahmed Al-Harrasi Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors Molecules 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids carbonic anhydrase-II α-glucosidase structure-activity relationship molecular docking |
| title | Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors |
| title_full | Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors |
| title_fullStr | Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors |
| title_full_unstemmed | Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors |
| title_short | Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors |
| title_sort | design synthesis and molecular docking study of novel 3 phenyl β alanine based oxadiazole analogues as potent carbonic anhydrase ii inhibitors |
| topic | 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids carbonic anhydrase-II α-glucosidase structure-activity relationship molecular docking |
| url | https://www.mdpi.com/1420-3049/27/3/816 |
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