Mathematical models of antisickling activities of benzoic acid derivatives on red blood cells of sicklers.

A classical drug design technique based on the quantitative structure--activity relationship is applied to a series of synthetic benzoic acid derivatives. Some of the active derivatives tested include; p-toluic acid, p-dimethyl-amino benzoic acid, p-fluorobenzoic acid, p-chlorobenzoic acid, m-chlorobenzoic acid, p-bromobenzoic acid, p-nitrobenzoic acid, and p-iodobenzoic acid. The Hansch lipophilicity, pi, and the Hammett electronic parameters; sigma, were found to predict activities of the agents on the reversal of sickle-shaped deoxygenated sickle red blood cell to normal morphology. A series of equations correlating the biological activities with the structure of the tested compounds were analysed using multiple regression techniques. The most applicable of the equations was found to be; Log BR = -A sigma + B pi--C pi 2 + K Interpretation of this equation in terms of the biological action of the drugs on red blood cells was attempted. In designing a potent antisickling agent, the benzoic acid should have strong electron donating group(s) attached to the benzene ring and should be made averagely lipophilic to satisfy the relationship derived in this study.