Advances in quantitative structure-activity relationship models of antioxidants

During the past decade a large number of reports described the roles of active oxygen species in the development or exacerbation of various kinds of diseases. The systemic antioxidant defense system often fails to control the excess free radicals. Such a condition necessitates external antioxidant supplementation either in the form of drugs or vitamins. Quantitative structure-activity relationship (QSAR) serves as an effective computational tool for search and design of active molecules that may eventually be synthesized and assayed.

This review presents the current knowledge about QSAR studies of diverse groups of molecules with free radical scavenging activity. The QSAR studies summarized here would help to understand the proper mechanism underlying the interaction between the free radicals and antioxidant molecules.

The primary determinant factors for potent antioxidant activity include the electronic distribution of the molecules together with their lipophilicity and size and orientation of the substituents attached to the parent molecules. The potency of the antioxidants depends on the degree of reactivity of these molecules with the nearby free radicals and the stability of the oxidized antioxidant molecules thus obtained. The nature of substitution at the parent moiety plays a key role in the design of antioxidant molecules.