Synthesis and in silico ADMET profiling of novel 5-arylidene-2-(2,3,5,6,7,8-hexahydroacridin-4(1H)-ylidene)-1,3-thiazolidin-4-ones

Abstract

The corresponding thiazolidone derivative was synthesized with a good yield by the reaction of 1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile with thioglycolic acid. It was found that this compound is present in DMSO in the form of two isomers, (2E)-2-(2,3,5,6,7,8-hexahydroacridin-4(1H)-ylidene)-1,3-thiazolidin-4-one and (2Z)-2-(2,3,5,6,7,8-hexahydroacridin-4(1H)-ylidene)-1,3-thiazolidin-4-one in a ratio of 9:1, respectively, whereas it is present only in the form of the E-isomer in chloroform. The corresponding 5-arylidene-2-(2,3,5,6,7,8-hexahydroacridin-4(1H)-ylidene)-1,3-thiazolidin-4-ones were obtained with good yields. Isolation of all products is not difficult and is carried out by simple filtration. The physicochemical and pharmacokinetic properties of the obtained compounds were predicted, and a comparative analysis of the obtained indicators with active drugs, pioglitazone and rosiglitazone was carried out by using ADMETlab 2.0 software. All tested compounds comply with the Lipinski rule. Additionally, toxicity, half-life, clearance, intestinal absorption and blood-brain barrier penetration potentials were compared. In most respects, the synthesized compounds are comparable to active drugs. The 1,3-thiazolidin-4-one derivatives characterized in the article are promising as building blocks for the organic synthesis and for further in vitro testing.