Synthesis and Evaluation of Novel Substituted Pyrimidine-2-Thiols and thier Bioisosters as Potential Antioxidants

Abstract

Oxidation is a chain of chemical reactions generating free radicals by transferring electrons from a substrate to an oxidizing agent. These free radicals are generated from toxic environmental pollutants, ionizing radiations, etc, leading to various diseases like aging, Alzheimer, cancer, inflammation, etc. Antioxidant enzymes Superoxide dismutase, Glutathione peroxidase and Catalase act as defense mechanisms in body. Vitamin C, Vitamin E, Glutathione, Ubiquinone, resveratrol, etc is some of the non-enzymatic antioxidants. Extensive literature review revealed that the synthetic derivatives of natural antioxidants like curcumin and resveratrol show considerably good antioxidant activity. Also, various pyrimidine derivatives have wide range of biological activity. Pyrrolopyrimidine provides antioxidant effect, while glutathione possessing thiol group acts as antioxidant in body. Hence novel substituted Pyrimidine-2-thiols and their bioisosteres Pyrimidine-2-ols and Pyrimidine-2-amines were designed and synthesized. The chalcones were synthesized by Clasein-Schmidt condensation between aromatic aldehydes and ketones. The synthesis of pyrimidine ring was then achieved by reaction of α, β-unsaturated ketones with amidines. Structure elucidation of the synthesized compounds was done by spectral analysis. The antioxidant activity of the synthesized compounds was determined by Nitric oxide, Superoxide, DPPH and Hydrogen peroxide radical scavenging activity using ascorbic acid (10μg/mL) as the reference standard. Compounds exhibited highest activity against superoxide even at considerably low concentration of 10 μg/mL. Compounds with hydroxy substituents exhibited good activity against DPPH and hydrogen peroxide radicals, while the molecules with electron withdrawing substituents were found to be active against nitric oxide radicals. Key words: Pyrimidine-2-thiols, Pyrimidine-2-ols, Pyrimidine-2-amines, Antioxidant