IN SILICO STUDY OF PHYSICOCHEMICAL PROPERTIES AND DRUG-LIKENESS OF O,O-DIARYLTHIOPHOSPHORIC ACID HYDRAZIDE MOLECULES

Abstract

Introduction. To predict the biological activity of novel compounds, computational methods are preferable to traditional experimental studies. This reduces development costs, shortens the time-to-market for new drugs, and eliminates the need for animal testing. In contrast to the well-documented carboxylic and aromatic hydrazides, phosphorus-containing hydrazides have not yet been the subject of systematic virtual screening. This highlights the relevance of applying in silico methods to O,O-diarylthiophosphoric acid hydrazides. Such an approach, supported by the robust framework of modern organic synthesis, opens new avenues for the rational design of highly potent pharmaceutical agents. The aim of the study – to evaluate the physicochemical parameters of O,O-diarylthiophosphoric acid hydrazide molecules using web-based resources and to predict the drug-likeness of these compounds. Research Methods. Open-source software packages SwissADME (http://www.swissadme.ch/) and pkCSM (https://biosig.lab.uq.edu.au/) were used. Results and Discussion. The bioavailability of the studied compounds was predicted using Lipinski’s and Veber’s rules. All parameters were within the acceptable limits (molecular weight, lipophilicity, number of Hydrogen bond acceptors, number of Hydrogen bond donors, number of rotatable bonds, and topological polar surface area). The tested compounds also passed Ghose’s drug-likeness filters, including the partition coefficient, molecular weight, molar refractivity, and total number of atoms. In predicting oral bioavailability, we considered the following physicochemical properties of the O,O-diarylthiophosphoric acid hydrazide molecules: lipophilicity, size, polarity, insolubility, flexibility, and unsaturation. All parameters fell within the optimal range, except for unsaturation. This, however, does not preclude high oral bioavailability of the compounds. Conclusions. Using in silico methods, it has been proven that the physicochemical parameters of the 7 studied O,O-diarylthiophosphoric acid hydrazides meet the Lipinski, Veber, and Ghose drug-likeness criteria.