Background: At present, more than 8000 sesquiterpene lactones have been isolated and described from natural sources, a significant part of which has cytotoxicity and antitumor activity. One of the practically available sesquiterpene lactones is arglabin, which, as a renewable material, is used for the synthesis of new compounds. The article presents data on the study of cytotoxicity and antitumor activity of the arglabin and its derivatives using molecular modeling methods and, in the experiment in vitro and in vivo.
Aim: The aim of this work is to study the cytotoxicity and antitumor activity of new compounds based on the sesquiterpene lactone arglabin using molecular modeling and experimental pharmacology.
Methods: ChemDraw programs and a set of AutoDock programs were used for computer simulation. Molecular docking was carried out using the Maestro graphical interface of the Schrödinger Suite software package (Schrödinger, LLC, New York, NY, 2017). Docking modes standard precision and XP (extra precision) were used. In in vitro experiments, the antitumor activity of compound samples was studied in models of 60 human tumor cell lines, and clonogenic C6 rat glioma cells. The antitumor activity of the samples was studied in experiments in vivo on white outbred rats with transplanted tumors and was evaluated by the inhibition of tumor growth and the magnitude of the increase in average life expectancy.
Conclusion: When studying the antitumor activity on 60 cell lines of tumor cells (NCI60), clonogenic cells of C6 rat glioma, a high antitumor activity of some arglabin derivatives was established. The connection between the structure of arglabin derivatives and their inhibitory effect on farnesyl protein transferase, topoisomerases -I and -II was studied.
Keywords: Antitumor activity; Arglabin; Cytotoxicity; Farnesyl protein transferase; Molecular docking; Sesquiterpene lactones; Topoisomerases -I and -II.