Design, synthesis, and correlation analysis of 7-substituted 4-hydroxyquinoline-3-carboxylic acids as inhibitors of cellular respiration.

Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and for their ability to inhibit malate dehydrogenase as an intracellular target enzyme model. Correlation analysis indicates that ascites cell inhibition is linearly related to pi and that malate dehydrogenase inhibition is linearly related to MR.