Inhibitory, biocompatible, and pharmacological potentiality of dammarenolic-acid derivatives towards α-glucosidase (3W37) and tyrosine phosphatase 1B (PTP1B)

Abstract

Dammarenolic-acid derivatives experimentally demonstrated possessing inhibition activity towards α-glucosidase might be used as the evidence to retrieve an inhibitory mechanism and subjected for computational screening on other diabetes-related proteins, e.g. tyrosine phosphatase 1B. Seven structures reported in our preceding work (denoted as 1-7) were subjected for an in silico investigation in this study on inhibitability towards protein structure PDB-3W37 by molecular docking simulation. The computer-based results see a good agreement with those from laboratory-based reports, with the order of static stability: 3-3W37 > 1-3W37 > 7-3W37 > 2-3W37 > 6-3W37 ~ 5-3W37 ~ 4-3W37 (negligible activity). Together, experiment-theory reveals the most promising candidates are 1-3 and 7. The in-theory order for most promising inhibitors regarding protein structure UniProt-PTP1B is: 1-PTP1B > 6-PTP1B > 4-PTP1B. Quantity-structure relationship analyses (i.e. QSARIS and ADMET) expect 1-3 as compounds with sufficient bio- and pharma-compatibility. Altogether, the results specify 1 as the most promising candidate for multi-purpose inhibition towards diabetes-based proteins, thus encouraging elevated efforts for validation and further development for application.