Protein–ligand molecular dynamics simulation (PL-MDS), ADMET analyses, and bioactivity studies of phytochemicals from Aloe Vera: an In-Silico novel antidiabetics drug discovery effort

Diabetics mellitus remains a major global health challenge with increasing prevalence and limited treatment efficacy, necessitating the search for novel therapeutic agents. The continuous rise in diabetes cases worldwide, coupled with the limitations of existing medications, underscores the urgent need for effective alternatives. This study employs computer-aided drug design approach (CADD) via molecular docking operation to study the inhibitory potential, toxicity, oral bioavailability, drug-likeness, and protein–ligand molecular dynamics simulation (PL-MDS) of 103 isolated phytochemicals from Aloe vera against the alpha-amylase receptor (PDB ID: 3BAJ) towards the identification of novel lead compounds as anti-diabetic agents. The ADMET SAR2.0 tool was used to evaluate the absorption, distribution, metabolism, excretion, and toxicity of the isolated phytochemicals, while SwissADME and PASS software were used to examine the oral bioavailability, drug-likeness, and bioactivity of selected lead compounds. The most potent and safest lead (chlorogenic acid, heterogenin, and 5-p-coumaroylquinic acid) and standard (Acarbose and rosiglitazone), in complex with the receptor were subjected to protein–ligand molecular dynamics simulation using GROMACS to validate the stability and interactions of the identified lead with the active site of the target receptor. The outcome of these operations favoured hecogenin (− 10.6 kcal/mol), chlorogenic acid (− 7.8 kcal/mol), and 5-coumaroylquinic acids (− 7.8 kcal/mol) as novel and potential inhibitors of the 3BAJ receptor. The identified lead possessed excellent binding affinities, drug-likeness, bioactivities, ADMET properties, and stable and effective interactions with the active site of the target. Thus, these novel compounds could be explored towards the development of new anti-diabetic medications.