Synthesis and in silico ADMET prediction of the properties of novel sulfonyl indole derivatives

Abstract

The article presents a method for synthesizing sulfonyl-derived indoles by rearranging the corresponding N-arylhydrazones through boiling in acetic acid saturated with dry hydrogen chloride and the addition of anhydrous zinc chloride. The ADMET resource was used to predict the pharmacokinetic indicators of absorption, distribution, metabolism, and excretion of the synthesized compounds. The study compared the predicted activity of synthesized compounds to that of active drugs containing an indole fragment, specifically indole-3-carbinol and diindolylmethane. The results indicate that the introduction of a sulfonyl group has a positive effect on the pharmacokinetic indicators of the synthesized compounds, which are comparable to those of the active drugs. Sulphonyl-derived indoles have the potential for oral administration due to their good indicators of intestinal absorption (0.009–0.097). Additionally, there is no negative effect on the central nervous system as indicated by their indicators of penetration through the blood-brain barrier (0.003–0.008). Furthermore, the compounds did not exhibit inhibition of cytochrome P450 (CYP) enzymes. Rats are potential candidates for further in vivo studies due to their low rates of mutagenicity, carcinogenicity, and acute toxicity.