Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors
AbstractDeposition of hydroxyapatite (HA) or alkaline phosphate crystals on soft tissues causes the pathological calcification diseases comprising of end-stage osteoarthritis (OA), ankylosing spondylitis (AS), medial artery calcification and tumour calcification. The pathological calcification is sy...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2163394 |
| _version_ | 1797400988220391424 |
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| author | Muhammad Naeem Mustafa Pervaiz Ali Channar Muhammad Sarfraz Aamer Saeed Syeda Abida Ejaz Mubashir Aziz Fatmah Ali Alasmary Hanadi Yaqob Alsoqair Hussain Raza Song Ja Kim Asad Hamad |
| author_facet | Muhammad Naeem Mustafa Pervaiz Ali Channar Muhammad Sarfraz Aamer Saeed Syeda Abida Ejaz Mubashir Aziz Fatmah Ali Alasmary Hanadi Yaqob Alsoqair Hussain Raza Song Ja Kim Asad Hamad |
| author_sort | Muhammad Naeem Mustafa |
| collection | DOAJ |
| description | AbstractDeposition of hydroxyapatite (HA) or alkaline phosphate crystals on soft tissues causes the pathological calcification diseases comprising of end-stage osteoarthritis (OA), ankylosing spondylitis (AS), medial artery calcification and tumour calcification. The pathological calcification is symbolised by increased concentration of tissue non-specific alkaline phosphatase (TNAP). An efficient therapeutic strategy to eradicate these diseases is required, and for this the alkaline phosphatase inhibitors can play a potential role. In this context a series of novel quinolinyl iminothiazolines was synthesised and evaluated for alkaline phosphatase inhibition potential. All the compounds were subjected to DFT studies where N-benzamide quinolinyl iminothiazoline (6g), N-dichlorobenzamide quinolinyl iminothiazoline (6i) and N-nitrobenzamide quinolinyl iminothiazoline (6j) were found as the most reactive compounds. Then during the in-vitro testing, the compound N-benzamide quinolinyl iminothiazoline (6g) exhibited the maximum alkaline phosphatase inhibitory effect (IC50 = 0.337 ± 0.015 µM) as compared to other analogues and standard KH2PO4 (IC50 = 5.245 ± 0.477 µM). The results were supported by the molecular docking studies, molecular dynamics simulations and kinetic analysis which also revealed the inhibitory potential of compound N-benzamide quinolinyl iminothiazoline (6g) against alkaline phosphatase. This compound can be act as lead molecule for the synthesis of more effective inhibitors and can be suggested to test at the molecular level. |
| first_indexed | 2024-03-09T02:02:25Z |
| format | Article |
| id | doaj.art-0e9128486c3343348db1df5543e29616 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:25Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-0e9128486c3343348db1df5543e296162023-12-08T03:24:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2022.2163394Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitorsMuhammad Naeem Mustafa0Pervaiz Ali Channar1Muhammad Sarfraz2Aamer Saeed3Syeda Abida Ejaz4Mubashir Aziz5Fatmah Ali Alasmary6Hanadi Yaqob Alsoqair7Hussain Raza8Song Ja Kim9Asad Hamad10Department of Chemistry, Quaid-i-Azam University, Islamabad, PakistanDepartment of Basic sciences and Humanities, Dawood University of Engineering and Technology, Karachi, PakistanCollege of Pharmacy, Al Ain Campus, Al Ain University, Al Ain, United Arab EmiratesDepartment of Chemistry, Quaid-i-Azam University, Islamabad, PakistanDepartment of Pharmaceutical Chemistry, The Islamia University of Bahawalpur, Bahawalpur, PakistanDepartment of Pharmaceutical Chemistry, The Islamia University of Bahawalpur, Bahawalpur, PakistanDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaDepartment of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of KoreaDepartment of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of KoreaFaculty of Pharmacy, Grand Asian University Sialkot, Sialkot, PakistanAbstractDeposition of hydroxyapatite (HA) or alkaline phosphate crystals on soft tissues causes the pathological calcification diseases comprising of end-stage osteoarthritis (OA), ankylosing spondylitis (AS), medial artery calcification and tumour calcification. The pathological calcification is symbolised by increased concentration of tissue non-specific alkaline phosphatase (TNAP). An efficient therapeutic strategy to eradicate these diseases is required, and for this the alkaline phosphatase inhibitors can play a potential role. In this context a series of novel quinolinyl iminothiazolines was synthesised and evaluated for alkaline phosphatase inhibition potential. All the compounds were subjected to DFT studies where N-benzamide quinolinyl iminothiazoline (6g), N-dichlorobenzamide quinolinyl iminothiazoline (6i) and N-nitrobenzamide quinolinyl iminothiazoline (6j) were found as the most reactive compounds. Then during the in-vitro testing, the compound N-benzamide quinolinyl iminothiazoline (6g) exhibited the maximum alkaline phosphatase inhibitory effect (IC50 = 0.337 ± 0.015 µM) as compared to other analogues and standard KH2PO4 (IC50 = 5.245 ± 0.477 µM). The results were supported by the molecular docking studies, molecular dynamics simulations and kinetic analysis which also revealed the inhibitory potential of compound N-benzamide quinolinyl iminothiazoline (6g) against alkaline phosphatase. This compound can be act as lead molecule for the synthesis of more effective inhibitors and can be suggested to test at the molecular level.https://www.tandfonline.com/doi/10.1080/14756366.2022.2163394Alkaline phosphatasesynthesisDFTmolecular dockingkinetic analysis |
| spellingShingle | Muhammad Naeem Mustafa Pervaiz Ali Channar Muhammad Sarfraz Aamer Saeed Syeda Abida Ejaz Mubashir Aziz Fatmah Ali Alasmary Hanadi Yaqob Alsoqair Hussain Raza Song Ja Kim Asad Hamad Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Alkaline phosphatase synthesis DFT molecular docking kinetic analysis |
| title | Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors |
| title_full | Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors |
| title_fullStr | Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors |
| title_full_unstemmed | Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors |
| title_short | Synthesis, kinetic studies and in-silico investigations of novel quinolinyl-iminothiazolines as alkaline phosphatase inhibitors |
| title_sort | synthesis kinetic studies and in silico investigations of novel quinolinyl iminothiazolines as alkaline phosphatase inhibitors |
| topic | Alkaline phosphatase synthesis DFT molecular docking kinetic analysis |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2163394 |
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