New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities

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 μM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to >1000 μM, 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 μg/mL as evident by less than 10% cell death after 3 h of incubation.

A series of biscoumarin derivatives were screened for their cytotoxicity and enzyme inhibition activity against phosphodiesterase 1 from snake venom, and human nucleotide pyrophosphatase phosphodiesterase-1. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to >1000 μM against the human recombinant phosphodiesterase 1 enzyme, and 8.0 to 1150 and 9.44 to >1000 μM against the snake venom phosphodiesterase 1. Most of the active compounds were found to be non-cytotoxic and non-competitive inhibitors.Figure optionsDownload as PowerPoint slide