Molecular Docking and ADMET-Based Screening of Cow Milk Derived Volatile Organic Compounds against Targets of Type-II Diabetes

Abstract

Nutraceuticals derived from milk and other sources play a significant role in the management of diabetes mellitus, particularly type 2 diabetes (T2DM). Milk contains a variety of volatile compounds, including ketones, esters, acids, aldehydes, and lactones, which contribute to its aroma and flavour. These compounds can be naturally present in milk or formed during processing, such as heat treatment or fermentation. These bioactive compounds, including proteins, lipids, and oligosaccharides found in milk, exhibit various biological activities that can aid in glycaemic control and reduce complications associated with diabetes. The objective of this study is to evaluate these compounds for pharmacophore studies and anti-diabetic properties. The reported volatile organic compounds from milk were pooled and analysed for their pharmacological bioactivities, like Lipinski’s rule of five and ADMET, while maintaining an oral bioavailability. Further, these compounds are evaluated in silico for their potential anti-diabetic, by targeting α-amylase and DPP-4 proteins with the standard FDA-approved drug molecule Metformin. Among 41 volatile compounds, 13 compounds passed the drug likeness; these compounds were studied for their anti-diabetic activity by target proteins. Molecular Docking analysis revealed that α-Amylase interacted with (Benzoic acid -5.5 kcal/mol, 2-Ethyl-hexanoic acid       -5.2 kcal/mol, 2-Amino-5-methylbenzoic acid -6 kcal/mol) and DPP-4 interacted with (Benzoic acid       -5.5 kcal/mol,            2-Ethyl hexanoic acid   -5.2 kcal/mol,   2-Amino-5-methylbenzoic acid               -6.1 kcal/mol). Compounds in the milk had better interactions in comparison with the standard drug. Overall, the integration of nutraceuticals into diabetes management strategies offers a promising complementary approach to conventional therapies, potentially leading to improved patient outcomes and quality of life.