Dolichocarpols G−X: Previously undescribed macrocyclic humulene sesquiterpenoids from Anaxagorea dolichocarpa

Abstract

Eleven previously undescribed macrocyclic humulene sesquiterpenoids, dolichocarpols G−Q (1−11), five undescribed bicyclic, dolichocarpols R−V (12−16) and two undescribed norsesquiterpenes, dolichocarpols W−X (17−18) were isolated from the roots of Anaxagorea dolichocarpa. Their structures were unequivocally determined by the analysis of NMR, HRESIMS, and IR data, along with NMR and ECD quantum-mechanical calculations, followed by the application of the DP4+ method. Most compounds possess an ether bridge between different carbons, whereas compounds 13/14 and 15/16 are diastereomers isomerized at C-7/C-10 and at C-7/C-10/C-12, respectively. The antineuroinflammatory activity of compounds 1−18 was tested in an LPS/IFN-γ-stimulated BV2 microglial cell line. Compounds 1, 5, 8, 9 and 14 significantly reduced nitric oxide (NO) levels in a concentration-dependent manner (25–200 μM). Moreover, possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via in silico studies. NO is known as an inflammatory mediator in neurodegenerative diseases; therefore, the effects of these compounds indicate their potential antineuroinflammatory activity.