Calpocalyx dinklagei Harms (Fabaceae) is a tropical medicinal tree, which is indigenous to Western Africa. A phytochemical study of this local plant species from its stem bark has led to the isolation of two previously undescribed aryl benzofuran derivatives, named dinklagein A and B, together with eight known compounds. Their chemical structures were elucidated by use of extensive spectroscopic methods (IR, HREI-MS and 1D and 2D NMR). Among all isolates, dinklagein A displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) in the lipopolysaccharide (LPS) induced RAW264.7 macrophages. SAR and molecular docking investigations on iNOS and previously undescribed compounds (dinklagein A and B) supported experimental data. Furthermore, dinklagein A dose dependently suppressed the LPS-stimulated iNOS expression at both mRNA and protein level. It also attenuated IL-1 beta release, mRNA expressions of IL-1 beta and COX-2 at low doses. These results suggest that dinklagein A can be developed as natural, multi-target agent against several inflammatory diseases. (C) 2017 Elsevier Ltd. All rights reserved.