Novel indole alkaloids from Raputia simulans

Raputia simulans is a neotropical Rutaceae growing in the Amazonian basin. Investigation of the dichloromethane extracts of the stem bark and roots revealed the extraordinary abundance of non polar indole secondary metabolites and resulted to the isolation of several new natural products bearing unconventionally substituted indole moieties. The isolation procedure involved FCPC fractionation and successful isolation of minor indole components in one step from the original extracts, as well as traditional MPLC and HPLC techniques. More than 15 indole metabolites were isolated, comprising of 8 new monomers and 7 new dimers. The new indole monomers are exclusively substituted in position 5 of the indole ring, characteristically lacking substitution in position 3, with oxidated sidechains of open-type or forming furan or dihydrofuran closed rings. Among the new dimers, the 4 novel raputindoles (A-D) possess two indole moieties bridged via a fused cyclopentyl unit whereas the 3 new caulindoles bear an unusual MOM substitution at the terminal methyl groups, found for the second time in a natural product. [1],[2]. The novel raputindoles A-D were tested for their inhibition against CDK2, GSK-3β and DYRK1 and found to have moderate activity (IC₅₀>10 µM).

Fig.1: Indole metabolites from Raputia simulans

References: 1. Makangara, J. et al. (2003) Phytochemistry 65: 227–232.

2. Wu, Y. et al. (2009)J Nat Prod 72: 204–209.