Design, Synthesis and Evaluation of Antioxidant Activity of New Heterocyclic Compounds

Abstract

Oxygen is imperative for life but, ironically triggers cellular damage by oxidizing a variety of biologically important molecules, including DNA, proteins, lipids, and carbohydrates. Cells reduce molecular oxygen to water for the generation of energy (ATP). During the process, small amounts of partially reduced reactive oxygen results in generation of free radicals. In low or moderate concentrations they are responsible for physiological functions but excess production of free radicals or decrease in antioxidant system causes oxidative stress. The consequences of oxidative stress construct the molecular basis of the development of cancer, neurodegenerative disorders, cardiovascular diseases, diabetes and autoimmune disorders. Antioxidants play a critical role in prevention of oxidative stress induced by excessive free radical generation. Extensive literature review revealed that curcumin is regarded as potent natural antioxidant and its activity is due to diaryl moiety in conjugation with diketone moiety. Semi synthetic analogues of curcumin, in which heterocyclic ring was incorporated in to the diketone moiety, showed good antioxidant property. The research strategy was focused on merging diaryl moiety in conjugation with diketone moiety and incorporation of indazole ring possessing certain metabolic soft spots vital for the exhibition of antioxidant act ivity. Synthesized target molecules possess certain metabolic soft centres for the protection of essential features vital for antioxidant activity. Synthetic protocol involved the conversion of substituted aldehydes in to α, β-unsaturated carbonyl compounds by Claisen Schmidt condensation. The second step involved the synthesis of indazole ring from α, β-unsaturated carbonyl compounds using Hydrazine hydrate and Phenyl hydrazine. Chan lam coupling was done to synthesise arylated analog of Indazole derivatives. Two series were synthesized as potential antioxidant heterocyclic compounds by inclusion of linker (cyclohexane and piperidine) between the diaryl moieties. Structure elucidation of the synthesized compounds was done by IR, Mass, Proton NMR spectroscopy. The newly synthesized compounds were screened for antioxidant activity by DPPH, Hydrogen peroxide, Super oxide and nitric oxide radical scavenging activity. Compounds with 4-methoxy and 3, 4-dimethoxy substituents displayed significant activity against DPPH, Nitric oxide and Hydrogen Peroxide radicals as compared to other