Twelve metabolites were obtained from the culture media of <i>Chaetomium nigricolor</i>, including a new furan derivative, methyl succinyl Sumiki's acid (<b>1</b>), and two new atropisomers of the previously reported bis-naphtho-γ-pyrones, (a<i>S</i>)-asperpyrone A and (a<i>S</i>)-fonsecinone A (<b>2</b> and <b>3</b>). The structures were elucidated by spectroscopic, chemical, and chiroptical techniques. Compounds <b>2</b> and <b>3</b> inhibited nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound <b>2</b> was found to inhibit nuclear factor-kappa B and c-Jun N-terminal kinase activation, in turn suppressing pro-inflammatory mediators and cytokines including nitric oxide, prostaglandin E<sub>2</sub>, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12.