In silico vs in vitro experiment in research of the natural kinase A inhibitors

Aurora A kinase is one of the serine-threonine kinases that control mitotic and meiosis processes in cells. In the literature, its overexpression is often associated with the occurrence of various neoplastic diseases [1]. The search for compounds that can inhibit the overexpression of this protein is one of the strategies that is a field of research in the field of pharmaceutical and medical sciences [2-3]. Most reports, however, focus on synthetic compounds. As part of the project, a significant group will be compounds of natural origin, primarily capsaicin and its derivatives capsaicinoids. Capsaicin as a compound with a potential to inhibit Aurora A kinase was selected because capsaicin supplementation had previously been shown to abolish resistance to cisplatin treatment induced by overexpression of Aurora A kinase [4]. Preliminary analyzes using molecular docking indicate that capsaicin may show just such a potential [5]. In the first stage of the project, using molecular docking to find potential Aurora A kinase inhibitors, a group of compounds (mainly of natural origin), showing structural similarities with capsaicin, will be tested. Among the compounds planned to be tested are natural and synthetic capsaicinoids (dihydrocapsaicin, homocapsaicin, nonivamide, arvanil, olvanil, capsiat), curcumin, piperine, allicin and zingerone. Molecular docking will be performed with the use of two packages - Surflex and AutoDock [6]. It will also include compounds known to be active on Aurora kinases, e.g. barasertib, alisertib, danusertib [7-8].
Molecular docking is currently one of the widely used methods in pharmaceutical sciences to describe the modeling, simulation and visualization of biological and medical processes using computers. Due to the relatively low financial and time costs, they are used as the first step before undertaking appropriate in vitro and in vivo experiments. Based on the results obtained from docking, it is planned to perform verifying in vitro tests. A test kit to evaluate the inhibition of Aurora A kinase (CycLex Aurora Family Kinase Assay / Inhibitor Screening Kit) will be performed. Such tests are commonly used in the evaluation of Aurora A inhibitors [9]. Although Aurora A kinase is a known protein and numerous experiments have been carried out on it for years, so far no combination of numerical and experimental methods has been used in the study of its inhibitors. The use of compounds of different structures will also allow to assess the influence of the structure of the molecule on the potential biological effect.This project is a continuation of the doctoral dissertation "Structural and physicochemical analysis of selected ligands of the TRPV1 receptor". As part of this dissertation, the structural analysis of capsaicin and its derivatives was carried out. The information on the crystal structure obtained during these studies will be the starting point for in silico analyzes. The arrangement and the interaction network formed by the inhibitor molecule bound by Aurora A kinase will serve as a benchmark for the results obtained with the test compounds. The research on biological activity will therefore be the next stage of research on capsaicin and its derivatives.