New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities

Bioorg Med Chem. 2006 Dec 1;14(23):8066-72. doi: 10.1016/j.bmc.2006.07.037. Epub 2006 Aug 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Coumarins / chemical synthesis
  • Coumarins / pharmacology*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Phosphodiesterase I / antagonists & inhibitors*
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases / antagonists & inhibitors*
  • Snake Venoms / enzymology

Substances

  • Coumarins
  • Enzyme Inhibitors
  • Snake Venoms
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • phosphodiesterase I, snake venom
  • Pyrophosphatases