From Antarctica to cancer research: a novel human DNA topoisomerase 1B inhibitor from Antarctic sponge Dendrilla antarctica

Abstract

Nature has been always a great source of possible lead compounds to develop new drugs against several diseases. Here we report the identification of a natural compound, membranoid G, derived from the Antarctic sponge Dendrilla antarctica displaying an in vitro inhibitory activity against human DNA topoisomerase 1B. The experiments indicate that membranoid G, when pre-incubated with the enzyme, strongly and irreversibly inhibits the relaxation of supercoiled DNA. This compound completely inhibits the cleavage step of the enzyme catalytic mechanism by preventing protein binding to the DNA. Membranoid G displays also a cytotoxic effect on tumour cell lines, suggesting its use as a possible lead compound to develop new anticancer drugs.

Keywords:

• Natural product
• topoisomerase
• cancer
• drug development

Disclosure statement

The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.

Additional information

Funding

This work and AO were supported by PNRA (The Italian National Antarctic Research Program) awarded by the Ministry for the Education, University and Scientific Research (MIUR), grant number PNRA18_00005-D. Field work in Antarctica was funded by the US National Science Foundation awards ANT-0838776 and PLR-1341339 (B.J.B.) from the Antarctic Organisms and Ecosystems program.