INDOLE DERIVATIVES IN DEVELOPMENT OF ANTICANCER AGENTS FOR THERAPY OF TUMORS WITH P-GLYCOPROTEIN-MEDIATED CHEMORESISTANCE

To overcome chemoresistance of tumors, an approach based on the combination of structural features of two active molecules targeted to different cellular targets in one molecule was proposed. Oncoprotein MDM2 and P-glycoprotein, a transporter determining chemoresistance of tumors, were considered as target proteins. Computer modeling allowed identifying small molecule compounds interacting with each of the two proteins. As a result of the synthesis of the compounds and their testing, it was possible to demonstrate the antitumor efficacy of indolinone derivatives on several cell lines. Additional in vitro methods confirmed the mechanisms of action of the compounds – p53-mediated apoptosis and inhibition of P-glycoprotein activity.