Deciphering the interactions of compounds from Allium sativum targeted towards identification of novel PTP 1B inhibitors in diabetes treatment: A computational approach

Diabetes has increased radically in recent decades globally. Diabetes mainly emerged as a major health care problem in the world, among which type-2 diabetes is the most common. Protein tyrosine phosphatase 1B (PTP1B) is an important target for treating type-2 diabetes. Discovering new and effective treatment options for type-2 diabetes is currently of high international health importance. It is therefore expedient to identify the bioactive compounds of plants with inhibitory activity against PTP1B for designing drugs against type-2 diabetes. In the present study, a computational technique was used to identify bioactive compounds isolated from Allium sativum with PTP-1B inhibitory activity. A molecular docking study was achieved utilizing the Glide-Ligand Docking panel of Maestro 12.5 with Schrödinger Suite 2020-3. The binding free energy of the receptor-ligand complex was calculated using the MM-GBSA Prime panel. Pharmacophore models were generated using the PHASE module and the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were assessed using SwissADME and PROTOX-II servers. The top three compounds are kaempferol, apigenin, and guanosine; with a binding affinity of −7.597, −7.263, and −6.655 kcal/mol compared with −7.155 kcal/mol demonstrated by the standard ligand. These lead compounds, like the standard ligand interacted with important amino acid residues like PHE 280, ASN 193, and GLU 276. The ADMET prediction revealed possible oral bioavailability and safety for kaempferol and apigenin. Hence, the results demonstrated that compounds from A. sativum could inhibit PTP1B and could be considered for experimental studies and the development of drugs against type-2 diabetes.