Abstract
Dolastatin 16, a marine cyclic depsipeptide, was initially isolated from the sea hare Dolabella Auricularia by Pettit et al. Due to the lack of information regarding its bioactivity, target identification becomes an indispensable strategy for revealing the potential targets and mechanisms of action of Dolastatin 16. Network pharmacology was utilized to identify targets associated with the disease, gene ontology, and KEGG pathways. The results highlighted Matrix Metalloproteinase-9 (MMP9) as a potential target of Dolastatin 16 through network pharmacology analysis. This target was found to be primarily involved in the TNF signaling pathway and in foot ulceration-associated diabetic polyneuropathy. Furthermore, the binding mode and dynamic behavior of the complex were investigated through molecular docking and molecular dynamics studies. In the docking study, a native ligand (a hydroxamate inhibitor) and (R)-ND-336 were employed as ligand controls, demonstrating binding energy values of - 6.6 and - 8.9 kcal/mol, respectively. The Dolastatin 16 complex exhibited a strong affinity for MMP9, with a binding energy value of - 9.7 kcal/mol, indicating its high potential as an inhibitor. Molecular dynamics also confirmed the stability of the MMP9-Dolastatin complex throughout the simulation process. Dolastatin 16 has the potential to act as an MMP9 inhibitor, offering promise for accelerating the wound healing process in diabetic foot conditions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-023-00161-5.