New pentandralactams from Vietnamese Ceiba pentandra (L.) Gaertn. and their anti-inflammatory activity via NO production inhibition

Abstract

A phytochemical study on the 70% ethanol extract of the stem bark of Vietnamese Ceiba pentandra (L.) Gaertn led to the isolation of the three new sesquiterpene alkaloids pentandralactams A (1), B (2), and C (3), along with the six known compounds thespesilactam (4), isohemigossylic acid lactone-2-methyl ether (5), alanense H (6), hibiscolactone A (7), 11-hydroxy-2-O-methylhibiscolactone A (8), and vavain 3′-O-β-D-glucoside (9). Their structures were elucidated through extensive spectroscopic analyses, including HR-ESI-MS, and 1D and 2D NMR. All isolates were tested for their ability to inhibit NO production in LPS-induced RAW 264.7 cells. The sesquiterpene alkaloids pentandralactams A–C (1 − 3) exhibited potent NO inhibition with IC₅₀ values of 8.03, 9.79, and 11.28 µM, respectively. In silico, compound 1 demonstrated the strongest binding affinity with iNOS enzyme with extensive π-π stacking, hydrophobic interactions, and a key hydrogen bond, without any unfavorable contacts. Compound 2 formed multiple hydrogen bonds in addition to π-π interactions, contributing to stable binding, though its broader interaction distribution may slightly affect its specificity. Compound 3 also engaged in essential π-π and hydrophobic contacts but exhibited an unfavorable acceptor-acceptor interaction with ASN370, potentially reducing its efficacy. These results highlight the potential of C. pentandra-derived compounds for further development as anti-inflammatory agents.

Graphical abstract