title: Coumarin sulfonates: New alkaline phosphatase inhibitors; in vitro and in silico studies.
abstract: A library of coumarin derived sulfonyl esters (1-38) was synthesized by reacting various hydroxy coumarins with different alkyl and aryl sulfonyl chlorides. All compounds were evaluated for their potential to inhibit alkaline phosphatases (hTNAP and hIAP). Most of the compounds were found to be inhibitors of APs. Compound 20 was found to be the most active hIAP inhibitor (IC50= 1.11 ± 0.15 μM), whereas, compound 13 was found to be the most active hTNAP inhibitor (IC50= 0.58 ± 0.17 μM). Detailed structure activity relationship studies (SAR), and molecular docking studies were carried out to identify structural elements necessary for AP inhibition, in addition to rationalize most probable binding site interaction of the inhibitors with the AP enzymes.
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Uzma
authors.initials: U
authors.lastname: Salar
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: khalid.khan@iccs.edu.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Syeda Abida
authors.initials: SA
authors.lastname: Ejaz
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
authors.affiliation: Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.
authors.forename: Mariya
authors.initials: M
authors.lastname: Al-Rashida
authors.affiliation: PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.affiliation: Department of Physics, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D013451:Sulfonic Acids; D000469:Alkaline Phosphatase
keywords: Alkaline phosphatase; Coumarins; Docking studies; Inhibitory activity; SAR; Sulfonates