On the Inhibitability of Natural Products Isolated from <i>Tetradium ruticarpum</i> towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study
Dao-Cuong To,
Thanh Q. Bui,
Nguyen Thi Ai Nhung,
Quoc-Toan Tran,
Thi-Thuy Do,
Manh-Hung Tran,
Phan-Phuoc Hien,
Truong-Nhan Ngu,
Phan-Tu Quy,
The-Hung Nguyen,
Huu-Tho Nguyen,
Tien-Dung Nguyen,
Phi-Hung Nguyen
Affiliations
Dao-Cuong To
Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong District, Hanoi 12116, Vietnam
Thanh Q. Bui
Department of Chemistry, University of Sciences, Hue University, Hue City 530000, Vietnam
Nguyen Thi Ai Nhung
Department of Chemistry, University of Sciences, Hue University, Hue City 530000, Vietnam
Quoc-Toan Tran
Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay District, Hanoi 122100, Vietnam
Thi-Thuy Do
Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay District, Hanoi 122100, Vietnam
Manh-Hung Tran
Faculty of Hi-Tech Agricultural and Food Sciences, Dong A University, Da Nang City 550000, Vietnam
Phan-Phuoc Hien
Institute of Applied Science and Technology, Van Lang University, Ho Chi Minh City 700000, Vietnam
Truong-Nhan Ngu
Department of Natural Sciences & Technology, Tay Nguyen University, Buon Ma Thuot, Dak Lak 630000, Vietnam
Phan-Tu Quy
Department of Natural Sciences & Technology, Tay Nguyen University, Buon Ma Thuot, Dak Lak 630000, Vietnam
The-Hung Nguyen
College of Agriculture and Forestry, Thai Nguyen University (TUAF), Quyet Thang 24119, Vietnam
Huu-Tho Nguyen
College of Agriculture and Forestry, Thai Nguyen University (TUAF), Quyet Thang 24119, Vietnam
Tien-Dung Nguyen
College of Agriculture and Forestry, Thai Nguyen University (TUAF), Quyet Thang 24119, Vietnam
Phi-Hung Nguyen
Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay District, Hanoi 122100, Vietnam
Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 μM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 μM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure–activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.
