| Autor: |
Mustafa MN; Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan., Channar PA; Department of Basic sciences and Humanities, Dawood University of Engineering and Technology, Karachi, Pakistan., Sarfraz M; College of Pharmacy, Al Ain Campus, Al Ain University, Al Ain, United Arab Emirates., Saeed A; Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan., Ejaz SA; Department of Pharmaceutical Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., Aziz M; Department of Pharmaceutical Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., Alasmary FA; Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia., Alsoqair HY; Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia., Raza H; Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea., Kim SJ; Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea., Hamad A; Faculty of Pharmacy, Grand Asian University Sialkot, Sialkot, Pakistan. |
| Abstrakt: |
Deposition 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 (IC 50 = 0.337 ± 0.015 µM) as compared to other analogues and standard KH 2 PO 4 (IC 50 = 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. |
