- Newly synthesised oxime and lactone derivatives from: Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: Experimental bioassay-based evidence and theoretical computation-based prediction
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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 (IC50 of 2.73 ± 0.05 μM) > 6c (IC50 of 4.62 ± 0.12 μM) > 6e (IC50 of 7.31 ± 0.11 μM), and the computation-based analysis confirmed this, i.e., 5 (mass: 416.2 aμ polarisability: 52.4 ?3; DS: -14.9 kcal mol-1) > 6c (mass: 490.1 aμ polarisability: 48.8 ?3; DS: -13.7 kcal mol-1) > 6e (mass: 549.2 aμ polarisability: 51.6 ?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. This journal is
- Bao, Nguyen Chi,Bui, Thanh Q.,Chi, Nguyen Linh,Dung, Nguyen Thi,Huynh, Lam K.,Nhung, Nguyen Thi Ai,Ninh, Pham Thi,Petrova, Anastasiya V.,Phuong Thao, Tran Thi,Quy, Phan Tu,Smirnova, Irina E.,Thi Thanh Hai, Nguyen,Van Loc, Tran,Van Sung, Tran
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p. 35765 - 35782
(2021/12/02)
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