New cassane-type diterpenoids from kernels of Caesalpinia bonduc (Linn.) Roxb. and their inhibitory activities on phosphodiesterase (PDE) and nuclear factor-kappa B (NF-κB) expression

Abstract

In this paper, chemical investigation on the chloroform soluble fraction of seed kernels of Caesalpinia bonduc resulted in the isolation of five new cassane diterpenoids: norcaesalpinin O (1), norcaesalpinin P (2), caesalpinin MQ (3), caesall O/P (4/5) and seven known compounds (6-12). Compounds structures were elucidated by ¹H NMR, ¹³C NMR, 2D NMR, HR-MS and ECD (electronic circular dichroism) spectral analysis. The characters for new compounds with the presence of an aromatized C ring or demethyl group at C-17 position in the structures were found. By means of bioactive screenings, the inhibitory effect on type-4 phosphodiesterase (PDE4, the target protein of asthma disease) and nuclear factor-kappa B (NF-κB) expression were valued. Compound 1 was found to exhibit moderate inhibitory activity on PDE4 and much better binding affinity than other structures by docking studies for interaction analyzing. Compounds 6, 10 and 11 displayed considerable inhibitory strength against NF-κB expression with inhibitory ratio 48.6%, 42.9% and 37.1% at 10 µM, respectively. The isolation of cassane-type diterpenoids with anti-inflammation activity from C. bonduc implied that this plant might be a good source for anti-inflammation agents finding.

Keywords: Caesalpinia bonduc; Cassane diterpenoids; Leguminosae; NF-κB; Type-4 phosphodiesterase.