title: Phenolic glyscosides, a new class of human recombinant nucleotide pyrophosphatase phosphodiesterase-1 inhibitors.
abstract: Cytotoxicity and kinetic studies of phenolic glycosides, benzoyl salireposide (1) and salireposide (2), isolated from Symplocos racemosa, were performed against phosphodiesterase I enzyme from snake venom and human nucleotide pyrophosphatase phosphodiesterase-1. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both enzymes. K(i) Values of compounds 1 and 2 were found to be 360 and 1000 microM, respectively, against human nucleotide pyrophosphatase phosphodiesterase, and 525 and 1100 microM, respectively, against snake venom phosphodiesterase. IC(50) values of compounds 1 and 2 are 90 microM +/- 0.04 and 383 microM +/- 0.03, respectively, against human nucleotide pyrophosphatase phosphodiesterase and 171 microM +/- 0.02 and 544 microM +/- 0.021, respectively, against snake venom phosphodiesterase. Both compounds were found to be nontoxic up to concentration of 500 microM/mL as >90% cells were viable after 3 h of incubation. These compounds are potential candidates for the therapy of arthritis.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi 75270, Pakistan. hej@cyber.net.pk
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Naheed
authors.initials: N
authors.lastname: Fatima
authors.forename: Muhammed Athar
authors.initials: MA
authors.lastname: Abbasi
authors.forename: Saima
authors.initials: S
authors.lastname: Jalil
authors.forename: Viqar Uddin
authors.initials: VU
authors.lastname: Ahmad
authors.lastname: Atta-ur-Rahman
mesh_terms: D000818:Animals; D006027:Glycosides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006027:Glycosides; D010636:Phenols; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom; D011755:Pyrophosphatases; C405782:nucleotide pyrophosphatase - phosphodiesterase I