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

[Image: see text] 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.