Marine sponges and microorganisms are the source of many promising bioactive products for use in the treatment of cancer. Multicompound libraries can be readily generated from these sources for comprehensive bioactivity and biosynthetic investigations. Prior studies into these organisms/communities involved examination of Zyzzya sponge metabolites and corresponding bacterial communities from this genus. One particularly potent compound was a makaluvamine extracted from a Zyzzya fulginosa sponge from Papua New Guinea was highly active on PANC-1 cells. Additional studies show that the key structure of malakuvamine and other related compounds is a pyrrolo[4,3,2-de]quinoline motif now seen in 100 similar natural products.
This invention, made in collaboration with researchers at the Henry Ford Health System describes Pyrrolo[4,3,2-de]quinolines derived from malakuvamine and highly active against PANC-1 cells
One particular analog, termed makulavamine J had an IC50 of 54 nM in PANC-1 cells and 120 nm in OVCAR-5 cells, while another analog, 15-O-acetyl makaluvamine J (structure above), had an IC50 of 81 nM in PANC-1 cells and an IC50 of 8.6 nM in OVCAR-5 cells.
Potential lead in cancer therapy
Derived from a natural product
|United States Of America||Issued Patent||11,020,488||06/01/2021||2017-263|
|Patent Cooperation Treaty||Published Application||2018/170019||09/20/2018||2017-263|
makulavamine, natural products chemistry, marine derived drugs, natural product analogs