Exploration of Cannabis constituents as potential candidates against diabetes mellitus disease using molecular docking, dynamics simulations and ADMET investigations

Abstract

Diabetes Mellitus is one of the deadliest diseases in the world, while the current medications against this disease like acarbose represent many side effects such as diarrhea and abdominal discomfort. Many studies based on natural plants used in traditional medicine were performed to find or invent new drugs to treat diabetes mellitus disease. The traditional drug design based on the synthesis and analysis of compounds wanted to study expenses a lot of time and the cost of the synthesis process, while we can resolve these problems by using computational methods that help us to predict the efficacity, stability, and pharmacokinetics properties as a main step in the drugs design chain. In this study, the virtual screening was performed on a set of 49 compounds extracted from cannabis plants by using molecular docking simulation to examine their ability to create a stable complex with the alpha-amylase inhibitor which reduces blood glucose levels in the human body. Acarbose, a widely used anti-alpha amylase activity, was employed as a reference medicine. Further, the selected compounds which showed good binding affinity were subjected to the ADMET screening to predict the pharmacokinetics properties, Additionally, molecular dynamics testing was done to confirm the outcomes. The result was that 50 compounds docked in the binding site of the alpha-amylase protein, and 25 of those compounds demonstrated the ability to create a stable complex with the target. While the ADMET analysis indicated that two substances amongst would have favorable oral bioavailability and pharmacokinetics characteristics.

Keywords

• Alpha-amylase
• ADMET
• Cannabis
• Molecular docking
• Molecular Dynamics