Abstract
Background. A 'rational' approach to Drug Design involves virtual screening of compounds at an early stage to identify hit compounds and filter out unpromising molecules. The known potential of thiazolidine and benzothiazole scaffolds and the confirmed biological activity of their derivatives prompted us to search for 'drug-like' compounds. Aim: primary screening and evaluation of the physicochemical and pharmacokinetic parameters of molecules using an online service. Materials and methods. Materials: 5-isatinylidene-substituted derivatives of N- (4-oxo-2-thioxothiazolidin-3-yl)-2-(2- oxobenzo[d]thiazol-3(2H)-yl)acetamide (17 compounds). Methods: a freely available Swiss web tool SwissADME, hosted at http://www.swissadme.ch/. This in silico method allows for rapid calculation of the physicochemical parameters of molecules, determination of their pharmacokinetic parameters, and assessment of 'drug-likeness' and oral bioavailability. Results. The computer modeling of a series of 5-isatinylidene-substituted derivatives of thiazolidine with a benzothiazole moiety is substantiated and implemented. In silico screening of the physicochemical and pharmacokinetic properties of the molecules enabled prediction of their 'drug-likeness' and oral applicability. The value of the compounds for medicinal chemistry was determined based on the predicted ADME (Absorption, Distribution, Metabolism, Elimination) properties. According to the results, the investigated derivatives successfully pass the Lipinski filter and are characterized by moderate bioavailability (BS = 0.55) and synthetic accessibility (SA = 3.73–4.63). Low oral bioavailability is due to deviations in the permissible range of physicochemical parameters responsible for molecule polarity and saturation. Introducing alkyl radicals (CH3 -, C2 H5 -, n-C3 H7 -, i-C3 H7 -) at the 5th and/or 1st positions of the isatinylidene moiety leads to slight improvements in these indicators. Further elongation or branching of substituents optimizes molecule saturation but does not normalize the polarity characteristic of orally available substances. The best bioavailability radars are associated with compounds 13 and 14, while compound 1, according to ADME criteria, can be considered the most similar to existing drugs. Conclusion. The predicted ADME profile of the 5-isatinylidene-substituted derivatives is sufficiently acceptable, with limitations related only to the oral route of administration. It is advisable to explore alternative administration routes, and for the development of orally available molecules, optimize the structure and conduct targeted synthesis of 'hit compounds' followed by thorough in vitro and in vivo studies