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

Malic acid derivatives from camu-camu ( Myrciaria dubia ) 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 ( S )-4-butoxy-2-hydroxy-4-oxobutanoic acid ( 1 ) and ( S )-4-butoxy-3-hydroxy-4-oxobutanoic acid ( 2 ) (84:16) were isolated and identified as a potent inhibitor of α-amylase (IC 50 = 11.69 ± 1.75 μg/mL) and α-glucosidase (IC 50 = 102.69 ± 4.16 μg/mL). The chemical structures were confirmed by HPLC-ESIMS and 1 H and 13 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 1 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.