Ruthenium(III) Complexes of NAMI-A Type with Ligands Based on Lonidamine and Bexarotene as Antiproliferative Agents

The search for new metal-containing antitumor agents is still carried out at present. Although platinum compounds are used in clinical practice, they show drawbacks such as high general toxicity and primary or acquired resistance. Ruthenium compounds showed the best potential among non-platinum antitumor agents, two of which—NAMI-A and KP1019 (КР1339)—are under clinical trials. In this work, we present the synthesis of full analogs of leader compound NAMI-A containing fragments of biologically active organic molecules, namely Lonidamine and Bexarotene. Electrochemical behavior of Ru(III) complexes has been studied and ease of reduction has been shown, which indicates the promise of their use as antitumor agents whose mechanism of action seems to be based on activation by metal atom reduction. The cytotoxicity of obtained complexes has been studied in vitro and IC 50 values have been determined. Two compounds have been selected for further study.