Evaluation of coumarin and their derivatives as Janus Kinase-3 inhibitors using a theoretical model

Abstract

For several years, cancer has increased in the population, being one of the main causes of death worldwide. This clinical pathology is associated with the activation/release of various biomolecules, including the Janus kinase family (JAKs). It is important to mention that some studies indicate that some JAK inhibitors (ruxolitinib and tofacitinib) may have a significant effect on some autoimmune diseases and cancer; however, some of these drugs can produce secondary effects such as herpes zoster, infectious, acute respiratory distress and others. The aim of this study was to evaluate the interaction of coumarin and its derivatives (compounds 2 to 24) with the JAK-3 surface. In this way, the Interaction of coumarin and their derivatives with JAK-3 was determined using the 3pjc protein and either decernotinib or tofacitinib drugs as theoretical tools on DockinServer program. The results showed differences in the aminoacid residues involved in the interaction of coumarin and their derivatives with 3pjc protein surface compared with decernotinib and tofacitinib. Besides, the inhibition constant (Ki) for coumarin derivatives 7, 9 and 10 was lower compared with tofacitinib. However, Ki was lower for 2, 5, 7, 8, 9, 10, and 24 compared with decernotinib. In conclusion, the coumarin derivatives 2, 5, 7, 8, 9, 10, and 24 could be good alternatives as JAK-3 inhibitors to decrease cancer cells growth.