Structure-activity relationships of benzohydroxamic acid inhibitors of ribonucleotide reductase

A structure-activity relationship study of 28 substituted benzohydroxamic acids that inhibit ribonucleotide reductase was undertaken to discern the structural features of the molecule contributing to the inhibitory potency of these compounds. An equation containing three molecular connectivity indexes, but not including Hammett sigma values, was developed which gives close correlation with observed values for ribonucleotide reductase inhibition. It is postulated that the inhibitory potency involves two parts of the benzohydroxamic acid molecule. One is the hydroxamic portion, which complexes with the metal component of the enzyme, providing a qualitative effect. The other is an interaction involving the benzene ring and its substituents and may provide the quantitative aspect of the observed inhibition values.