title: New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities.
abstract: Biscoumarin derivatives 1-27 were tested for their inhibition of snake venom and human nucleotide pyrophosphatase phosphodiesterase-1 enzymes. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both the enzymes. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to > 1000 microM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to > 1000 microM, respectively, against snake venom phosphodiesterase. Compounds 1, 3, 4, 6, 7, 17, 26, and 30 were found to be non-competitive and non-cytotoxic upto a concentration of 200 microg/mL as evident by less than 10% cell death after 3 h of incubation.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, 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: Khalid M
authors.initials: KM
authors.lastname: Khan
authors.forename: Saima
authors.initials: S
authors.lastname: Jalil
authors.forename: Sajjid
authors.initials: S
authors.lastname: Iqbal
authors.lastname: Atta-Ur-Rahman
mesh_terms: D016923:Cell Death / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D012910:Snake Venoms / Q000201:enzymology
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D012910:Snake Venoms; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; C470790:phosphodiesterase I, snake venom; D011755:Pyrophosphatases