Synthesis of 4-substituted 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides and study of their ability to inhibit protein kinase C-α, prevent development of multiple drug resistance of tumor cells and cytotoxicity

A series of 3-[3-(dialkylaminomethyl)indol-1-yl]maleimides containing the indole, dihydroindole, mercaptophenol, or tetrahydroquinoline residues at position 4 of the maleimide ring, as well as 3-(dialkylaminomethyl)indole derivatives have been synthesized. Their ability to inhibit in vitro protein kinase C-α (PKC-α) has been studied. Cytotoxicity of new compounds and their ability to constrain activation of multiple drug resistance (MDR) have been studied in the human tumor cell line. Both the toxic and the low-toxic PKC-α inhibitors prevent the activation of MDR in the tumor cells. Among compounds under study, a number of substances have been found that prevent the activation of MDR but do not inhibit PKC-α.