Mono--butyl Malate-Derived Compounds from Camu-camu () Malic Acid: The Alkyl-Dependent Antihyperglycemic-Related Activity.

Malic acid derivatives from camu-camu () fruit exhibited a strong in vitro inhibitory activity toward pancreatic α-amylase and α-glucosidase enzymes. During a bioguided chromatographic fractionation process of the whole fruit (pulp and peelings) polar extract, isomers ()-4-butoxy-2-hydroxy-4-oxobutanoic acid () and ()-4-butoxy-3-hydroxy-4-oxobutanoic acid () (84:16) were isolated and identified as a potent inhibitor of α-amylase (IC= 11.69 ± 1.75 μg/mL) and α-glucosidase (IC = 102.69 ± 4.16 μg/mL). The chemical structures were confirmed by HPLC-ESIMS and H and C NMR (one- and two-dimensional) analyses. The structure-based virtual screening demonstrated that the aliphatic moiety plays a significant role in the binding mode of the test alkyl malate esters. Compound exhibited the best interaction profile to bind both enzymes, having key structural features to form relevant contacts by involving adequate enzyme-ligand complex stabilization and compactness over time.