title: Identification of novel chromone based sulfonamides as highly potent and selective inhibitors of alkaline phosphatases.
abstract: A new series of structurally diverse chromone containing sulfonamides has been developed. Crystal structures of three representative compounds (2a, 3a and 4a) in the series are reported. All compounds were screened for their inhibitory potential against alkaline phosphatases (ALPs). Two main classes of ALP isozymes were selected for this study, the tissue non-specific alkaline phosphatase (TNALP) from bovine and porcine source and the tissue-specific intestinal alkaline phosphatases (IALPs) from bovine source. All sulfonamide compounds had a marked preference for IALP (K(i), up to 0.01 ± 0.001 μM) over TNALPs. Kinetics studies of the compounds showed competitive mode of inhibition. Molecular docking studies were carried out in order to characterize the selective inhibition of the compounds. An additional interesting aspect of these chromone sulfonamides is their inhibitory activity against ecto-5'-nucleotidase enzyme.
authors.affiliation: Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, 54600 Lahore, Pakistan. maria_al_rashida@hotmail.com
authors.forename: Mariya
authors.initials: M
authors.lastname: al-Rashida
authors.forename: Rabia
authors.initials: R
authors.lastname: Raza
authors.forename: Ghulam
authors.initials: G
authors.lastname: Abbas
authors.forename: Muhammad Shakil
authors.initials: MS
authors.lastname: Shah
authors.forename: George E
authors.initials: GE
authors.lastname: Kostakis
authors.forename: Joanna
authors.initials: J
authors.lastname: Lecka
authors.forename: Jean
authors.initials: J
authors.lastname: Sévigny
authors.forename: Muhammad
authors.initials: M
authors.lastname: Muddassar
authors.forename: Constantina
authors.initials: C
authors.lastname: Papatriantafyllopoulou
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002867:Chromones / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D000469:Alkaline Phosphatase
keywords: ALP; Alkaline phosphatase inhibitors; Chromones; Ecto-5′-nucleotidase inhibitors; IALP; Molecular docking; Structure activity relationships (SARs); Sulfonamides; TNALP; alkaline phosphatase; ecto-5′-NT; ecto-5′-nucleotidase; intestinal alkaline phosphatase; tissue non specific alkaline phosphatase