Hybrid Molecules of Hydroxycinnamic and Hydroxybenzoic Acids as Antioxidant and Potential Drug: A DFT Study

Abstract

AbstractDue to the disruption of homeostasis, the amount of free radicals produced may increase during metabolic processes leading to oxidative stress and may cause numerous diseases. Antioxidant prevents oxidative stress. Here, we have designed twenty hybrid antioxidant molecules which are also potential drugs. These molecules are mainly hybrids of hydroxybenzoic acids and hydroxycinnamic acids. At first, we have carried out a conformational analysis to find out the most stable structure of the molecules. Conformational studies are performed with the MP2 method. Thereafter, the physicochemical parameters are calculated, showing that these molecules are probable antioxidants. Further, we have investigated the free radical scavenging capacity of these molecules for inactivating eight prototype oxyradicals. The scavenging capacity was estimated by considering Gibbs free energy for the three mechanisms, viz. HAT, SPLET, and SET‐PT. Our study on mechanisms shows that for these molecules HAT and SPLET are favorable in the gas phase, while in solvent medium HAT and SET‐PT are competitive. An empirical rule for combining such hydroxycinnamic and hydroxybenzoic acids is proposed. In addition, the druglikeness of the molecules is calculated using Lipinski's rule of five. The advantage of our set of designed hybrid molecules is that they show antioxidant behavior with pharmacophoric characteristics. Thus, the set of promising antioxidants with drug‐like properties could create new prospects in drug discovery.