Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles
In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid...
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doaj-538ddfc67a0a4bd5bec5d97ce24650ae2020-11-24T22:32:07ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-03-01610.3389/fchem.2018.00061337318Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and OxadiazolesAliya Ibrar0Ajmal Khan1Ajmal Khan2Majid Ali3Rizwana Sarwar4Saifullah Mehsud5Umar Farooq6Syed M. A. Halimi7Imtiaz Khan8Imtiaz Khan9Ahmed Al-Harrasi10Department of Chemistry, Abbottabad University of Science & Technology, Havelian, PakistanDepartment of Chemistry, COMSATS Institute of Information Technology, Abbottabad, PakistanUoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Nizwa, OmanDepartment of Chemistry, COMSATS Institute of Information Technology, Abbottabad, PakistanDepartment of Chemistry, COMSATS Institute of Information Technology, Abbottabad, PakistanDepartment of Chemistry, Abbottabad University of Science & Technology, Havelian, PakistanDepartment of Chemistry, COMSATS Institute of Information Technology, Abbottabad, PakistanDepartment of Pharmacy, University of Peshawar, Peshawar, PakistanDepartment of Chemistry, Quaid-i-Azam University, Islamabad, PakistanSchool of Chemistry, Cardiff University, Cardiff, United KingdomUoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Nizwa, OmanIn a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 μM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 μM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 μM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 μM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of −10.19, −9.97, −9.68, and −11.03 Kcal.mol−1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a–h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of −9.9, −7.4, and −8.2 Kcal.mol−1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.http://journal.frontiersin.org/article/10.3389/fchem.2018.00061/fullcoumarin thiazolescoumarin oxadiazolescholinesterase inhibitionmolecular dockingMOE score |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aliya Ibrar Ajmal Khan Ajmal Khan Majid Ali Rizwana Sarwar Saifullah Mehsud Umar Farooq Syed M. A. Halimi Imtiaz Khan Imtiaz Khan Ahmed Al-Harrasi |
spellingShingle |
Aliya Ibrar Ajmal Khan Ajmal Khan Majid Ali Rizwana Sarwar Saifullah Mehsud Umar Farooq Syed M. A. Halimi Imtiaz Khan Imtiaz Khan Ahmed Al-Harrasi Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles Frontiers in Chemistry coumarin thiazoles coumarin oxadiazoles cholinesterase inhibition molecular docking MOE score |
author_facet |
Aliya Ibrar Ajmal Khan Ajmal Khan Majid Ali Rizwana Sarwar Saifullah Mehsud Umar Farooq Syed M. A. Halimi Imtiaz Khan Imtiaz Khan Ahmed Al-Harrasi |
author_sort |
Aliya Ibrar |
title |
Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles |
title_short |
Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles |
title_full |
Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles |
title_fullStr |
Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles |
title_full_unstemmed |
Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles |
title_sort |
combined in vitro and in silico studies for the anticholinesterase activity and pharmacokinetics of coumarinyl thiazoles and oxadiazoles |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Chemistry |
issn |
2296-2646 |
publishDate |
2018-03-01 |
description |
In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 μM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 μM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 μM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 μM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of −10.19, −9.97, −9.68, and −11.03 Kcal.mol−1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a–h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of −9.9, −7.4, and −8.2 Kcal.mol−1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction. |
topic |
coumarin thiazoles coumarin oxadiazoles cholinesterase inhibition molecular docking MOE score |
url |
http://journal.frontiersin.org/article/10.3389/fchem.2018.00061/full |
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