In silico and in vitro study of antithyrosinase activity of new schiff bases - azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

Introduction. Skin hyperpigmentation is an important problem of dermatocosmetology. The resulting pigment spots on the skin of a person, especially in open areas of the body, affect their psychoemotional state and social adaptation, and in some cases trigger dermatological diseases. The aim of the study is to search for new effective and safe compounds with anti-tyrosinase activity. Materials and methods. Seven new previously synthesized azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide are the objects of research. To study in silico the molecular mechanisms of tyrozinase inhibition by the compounds under study, the method of molecular annealing was used. The inhibitory activity of tyrosinase was determined according to the method by Mapunya et al. (2012). Results. During the computational experiment, we determined amino acid residues of the active tyrosinase site, with which azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide interact. In vitro evaluation of the anti-tyrosinase activity of the studied compounds indicated that almost all the analyzed substances were inferior to the referents in terms of the strength of biological action, except for compound 1, which was superior in activity to kojic and lactic acids. Based on the LD50 value of compound 1, it was assigned to the 5th class of toxicity according to the GHS classification. Conclusion. In the course of the conducted research, it was found that structure 1 surpasses kojic and lactic acids in the severity of its pharmacological activity. We consider it appropriate to further pharmacological studies of this substance.