Phenylspirodrimanes (PSD) are the
sesquiterpene quinone type meroterpenoids found in nature. PSDs are found to exhibit inhibitory activity against immunocomplex diseases, and
tyrosine kinase receptors. Three of the different PSDs C1, C2, and C3 that have been reported to be isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308 are selected for studying their possible inhibitory effect against
type 2 diabetes mellitus. Mechanistically, blocking
protein tyrosine phosphatase 1B (PTP1B) helps to reduce the
insulin resistance induction caused by the high expression of PTP1B. The QSAR, ADME, toxicity (T) study was carried out to predict the pharmacokinetic properties and the
biological activities of the PSDs. PASS prediction web tool was used to find and select the target
proteins 1NNY, and 2HNP. According to the molecular docking simulations, C1 and C2 showed better binding affinity of -8.5 kcal/mol, and -8.1 kcal/mol respectively against 1NNY compared to the control
ligand. RMSD, RMSF, Rg, and SASA analysis revealed that both C1, and C2 showed better stability, minor conformational changes, and minor fluctuation upon binding to PTP1B.
Protein contact analysis was carried out to validate the residues that are in contact with the
ligands according to molecular docking studies. Overall, C1, and C2 could be proposed as novel natural hits to be developed and small modifications of these PSDs could result in inducing the binding affinity significantly, although experimental validation is required for further evaluation of the work.Communicated by Ramaswamy H. Sarma.