Cytotoxic 4-nerolidylcatechol from Pothomorphe peltata inhibits topoisomerase I activity

Bioactivity-guided fractionation of the leaf methanolic extract of P. peltata (Piperaceae), using the brine shrimp lethality test, led to the isolation of catechol derivative 4-nerolidylcatechol (4-NC). The methanolic extract was active against crown gall tumour in potato discs, showing a 22% crown gall tumour inhibition (SD = 4%), while 4-NC was cytotoxic against KB tumour cells growth (EC50 = 1.3 micrograms/ml). No interaction with DNA could be observed when tested using the methyl green-DNA (MG-DNA) bioassay. An inhibition in the activity of topoisomerase I using agarose gel electrophoresis was detected in the presence of the purified compound (IC50 = 20 micrograms/ml), suggesting that this could be a possible mechanism for the cytotoxicity observed in KB cells.