In silico analysis of 2'-aminochalcone derivatives: bioavailability, acute toxicity and pharmacokinetics

One of the instruments of medicinal chemistry of the XXI century is the application of in silico analysis of a number of pharmacological characteristics of compounds. Primary screening represents an important stage of preclinical studies and in some cases helps to evaluate the feasibility of further development of new biologically active compounds. In this work, in silico evaluation of bioavailability and prediction of pharmacokinetics of 2'-aminochalcone derivatives was performed using the online resource SwissADME (SwissDrugDesign). Based on the data obtained using online services Way2Drug Gusar, admetSAR 3.0, Deep-PK, and ProTox-3.0, the LD50 value at oral administration was estimated on the model of rat organism with subsequent assignment of the studied compounds to a certain class of toxicity in accordance with the globally harmonized system of classification and labeling of chemical substances (GHS). The studied 2'-aminochalcone derivatives were obtained by the Kleisen-Schmidt condensation reaction under sonochemical activation conditions followed by their acylation and interaction of a number of acylated derivatives with the corresponding amine; the structure of the target compounds was confirmed by NMR and IR spectroscopy data, and also by HPLC-MS. As a result, it was found that all obtained compounds conform to the empirical rules of Lipinski and Weber, which may indicate their potentially acceptable bioavailability in oral administration. Analysis of acute cytotoxicity showed that all studied compounds may belong to class IV toxicity. Prediction of pharmacokinetics of the studied compounds showed that all derivatives of 2'-aminochalcone obtained may have a high probability of absorption through the GI tract, ability to diffuse through the BBB, lack of inhibitory activity of P-glycoprotein and are not a substrate for this protein. All investigated derivatives of 2'-aminochalcone can potentially be inhibitors of the activity of various isoforms of cytochrome P450, and also do not show inhibitory action with respect to transporter proteins OATP1B1, OATP1B3 and OATP2B1. Contribution of the authors: the authors contributed equally to this article. The authors declare no conflicts of interests.

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