VIRTUAL SCREENING AND PREDICTION OF ADME PERAMETERS OF A SERIES OF 5-ARYLIDENE SUBSTITUTED DERIVATIVES OF RHODANINE WITH BENZOTHIAZOLE MOIETY IN THE MOLECULES
Authors: Mosula L. M. , Mosula V. S. 
Published: January 2025

The knowledge of the ADME profile of the active substance’s molecules is important in the development of new drugs. Before starting the synthesis, it is advisable to determine the value of the compounds for medicinal chemistry and to predict their bio- and synthetic availability. For the assessment of the drug-like properties of the molecules, it is necessary to determine their physicochemical and pharmacokinetic properties. The 2-thioxothiazolidin-4-one (rhodanine) derivatives are interesting in pharmacological terms, as their diverse activity is influenced by the 5-arylidene moiety. It is known that they have antiviral, antidiabetic, anticonvulsant and other types of biological activity. In order to find effective ligands that have affinity for several biotargets, it is advisable to combine the so-called privileged structures in one molecule. One of such molecules with a wide range of biological effects (antitumor, antiviral, antituberculosis and other) is benzothiazole. A considerable number of possible ways for the structure modification of these heterocycles prompted us to study them in depth. The preliminary studies allow us to state that the combination of 5-arylidene-substituted 4-thiazolidine scaffold with a benzothiazole moiety is a viable approach to create drug-like molecules. In continuation of our previous studies, we decided to use an open access in silico tool to calculate the molecular descriptors of the studied compounds in order to predict their behaviour inside the human body, and to thoroughly study the most promising ones in vitro and in vivo in the future.
The aim of the research. On the basis of the molecular structure of differently substituted 5-arylidene thiazolidine derivatives with a benzothiazole moiety at the 3-position of the basic heterocycle, perform in silico prediction of their ADME parameters.
Materials and methods. On the basis of the pharmacological potential of the lead compound (N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetamide), 17 differently substituted 5-arylidene derivatives were selected for virtual screening. To determine the physicochemical and pharmacokinetic parameters of the molecules, their drug-like properties and suitability for medicinal chemistry, we used the SwissADME web service, which is in open access.
Research results. We have studied the effect of aryl substituents at position 5 of the rhodanine cycle on the peroral availability of molecules, predicted the absorption, distribution, metabolism and excretion of compounds. The obtained prognosis data indicate the viability of the search for promising compounds with optimal physicochemical and pharmacokinetic parameters for medicinal chemistry among rhodanine derivatives with a benzothiazole moiety in the molecules. All the investigated derivatives are characterised by sufficient drug-like properties with moderate bioavailability and easy synthesis, and compound 8 is predicted to have the best ADME profile.
Conclusions. The in silico prediction results outline a plan of further actions for the targeted synthesis of compounds and experimental confirmation of the data obtained. To optimise the ADME profile, we plan to carry out structural modification of the compounds. A promising direction we consider is the modification of the 5-arylidene moiety by introducing potential pharmacophore groups. The search for pharmacologically active compounds among rhodanine derivatives with a benzothiazole moiety is ongoing.