Newly synthesised oxime and lactone derivatives from Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction.

Dipterocarpus alatus -derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a-3m) and 7 lactones (4, 5, 6a-6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a-3m, 4, 5, and 6a-6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC 50 of 2.73 ± 0.05 μM) > 6c (IC 50 of 4.62 ± 0.12 μM) > 6e (IC 50 of 7.31 ± 0.11 μM), and the computation-based analysis confirmed this, i.e. , 5 (mass: 416.2 amu; polarisability: 52.4 Å 3 ; DS: -14.9 kcal mol -1 ) > 6c (mass: 490.1 amu; polarisability: 48.8 Å 3 ; DS: -13.7 kcal mol -1 ) > 6e (mass: 549.2 amu; polarisability: 51.6 Å 3 ; DS: -15.2 kcal mol -1 ). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation.