In silico screening of Annona muricata L. Leaf Constituents and Derivatives Towards Selected Targets of Type 2 Diabetes Mellitus

Abstract

Background: Type 2 diabetes mellitus, or T2DM, is one of the world's most chronic health problems that is linked to numerous deaths and high health care expenses. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), protein-tyrosine phosphatase 1B (PTP1B) and mono-ADP-ribosyl transferase sirtuin-6 (SIRT6) were among the novel proteins and focus targets of diabetes research. Annona muricata is a commonly used natural remedy for several illnesses, including type 2 diabetes mellitus. However, most of these traditional claims have received few molecular evaluations.

Objectives: This investigated the phytoconstituents and derivatives of the leaves of A. muricata by evaluating their binding profiles towards selected novel T2DM-related protein targets through in silico methods.

Methodology: This study screened the potential lead compounds from the leaves of A. muricata by evaluating the binding energies of the parent compounds and derivatives with the targets compared to the native ligands and known substrates through molecular docking simulations. Additionally, pharmacokinetic, physicochemical properties, and binding interactions were also assessed using several software programs and online databases.

Results: Out of the 8 selected parent compounds of Annona muricata, a total of 672 derivatives were designed, tested, and compared against the controls for at least one of the three protein targets. Among these, 280 derivatives exhibited more negative binding energies than controls in each protein target.

Conclusion: The designed derivatives can be synthesized and further investigated for potential biological effects towards 11β-HSD1, PTP1B, and SIRT6 through in vitro and in vivo experiments.