Phenolic glyscosides, a new class of human recombinant nucleotide pyrophosphatase phosphodiesterase-1 inhibitors.
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.
Choudhary
Muhammad Iqbal
MI
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi 75270, Pakistan. hej@cyber.net.pk
Fatima
Naheed
N
Abbasi
Muhammed Athar
MA
Jalil
Saima
S
Ahmad
Viqar Uddin
VU
Atta-ur-Rahman
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
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