Towards alternative treatment for type 2 diabetes: An in silico analysis of sponge-derived marine bioactive compounds on PTP1B and DPP-4

Type 2 Diabetes is a medical condition involving pathophysiological manifestations of atypical blood glucose levels due to impaired insulin receptor sensitivity. Factors such as genetic makeup and lifestyle predispose individuals to develop such a chronic disease. As the number of Type 2 Diabetes cases increases each year, there is a proportional necessity to design and develop drugs that are competent with respect to the existing market. Marine-derived compounds, specifically that of sponge origin hold great potential due to their biological and chemical diversity. In this study, 50 of them were examined for their bioactivity towards Type 2 Diabetes targets, Dipeptidyl Peptidase-4 (DPP-4) and Protein Tyrosine Phosphatase 1B (PTP1B). The compounds were subjected to a number of in silico analyses starting with molecular docking to assess and rank them based on the lowest binding free energy scores. From there, the top 10 compounds for each drug target were subjected to ADMET profiling and interaction analyses to characterize drug-likeness and determine participating residues within the binding pocket. Cumulatively, the results obtained from the aforementioned analyses narrowed down to (S)-6’-debromohamacanthin B (DB1) as a potential multi-target inhibitor towards DPP-4 and PTP1B. Validity of such a claim was confirmed through molecular dynamics simulations