Topological sub-structural molecular design approach: Radical scavenging activity

In the last decades phenolic compounds have gained enormous interest because of their beneficial health effects such as anti-inflammatory, anticancer, or antiviral activities. The pharmacological effects of phenolic compounds are mainly due to their antioxidant activity and their inhibition of certain enzymes. This antoxidant activity is related to the structure and has been extensively reported throught SAR or QSAR models. These studies confirmed that the number and position of hydroxyl groups, the related glycosylation and other substitutions in the phenolic ring largely determined radical scavenging activity. Most of these models are based on certain families of chemicals (flavonoids, cinnamic acids, etc…) and the model by itself is not useful for other substances of a different family. In this study we developed a QSAR model for a heterogeneous group of substances with TOPS-MODE descriptors for an interpretation of the antioxidant activity of these compounds in the form of bond contributions. The model developed, able to describe more than 90% of the variance in the experimental activity, also has a good predictive ability and stability. The information extracted from the QSAR model revealed that the major driving forces for radical scavenging activity are hydrogen bond donation and polarity. With this work we have managed to unify the different families of antioxidants in a single model with sufficient capacity to make predictions of radical scavenging activity for unknown substances.

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► We unify the different families of antioxidants in a single QSAR model.
► The model developed has a good predictive ability and stability.
► This model has the ability to interpret the antioxidant activity in form of bond contributions.