ADMET and Druglikeness Calculations of Sarin, Soman, and Their Hypothetical Derivatives

Abstract

Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) represents a numerical classification of any chemical to be a drug candidate with promising therapeutic efficacy with minimum toxicity or sensitivity depending on its chemical structures and its physicochemical properties. Sarin (GB) and Soman (GD) are nerve agents classified as chemical warfare agent containing phosphorous atom. Acetylcholine (ACh) as a neurotransmitter esterifies by acetyl cholinesterase enzyme (AChE) that can be irreversibly inhibited by (GB and GD) meaning termination of muscle function. Here, new in Silico predication of two nerve agents (Sarin and Soman) was done. These organophosphorous agents were hypothetically subjected to a reaction with lactic acid and various amino acids. New P-O with lactic acid and P-N linkage was between Sarin or Soman and different amino acids. Both reactions were through fluorine atom with hydroxyl group (P-O formation) and with amine (P-N). The ADMET and Druglikeness properties of the parent chemical warfare agents and their hypothetical products were subjected to MarvinSketch program and preadmet website. Sarin and Soman and their hypothetical products showed many noticeable characters such as: all 20 tested compounds were with non- inhibition character of Pgp and CYp-2D6; substrate character with CYP-3A4, negative values to skin permeability, negative to Carcino-Mouse, low risk to hERG inhibition. Other calculated predictors were varied in response between all calculated compounds.