Synethesis and Biological Evaluation of Morpholino Substituted Styryl-Phenyl Pyrimidines and Piperidinyl Substituted Styryl-Phenyl Pyrimidines Antioxidants

Abstract

Oxidation is a reaction in which mainly free radicals are generated by transferring of electrons from substrate to oxidizing agent. The source of free radicals is toxic environmental pollutants, ionizing radiation, heavy metal poisoning etc. There are various types of free radicals like hydrogen free radical, reactive oxygen species (ROS), reactive nitrogen species (RNS) etc. The human body converts a small amount of the oxygen that we breathe into free radicals that are essential to ward off diseases. Literature review suggested that curcumin and resveratrol are good natural antioxidants and their activity is due to diaryl moiety in conjugation with diketone moiety and stilbene moiety respectively. Semisynthetic analogues of curcumin in which heterocyclic ring was incorporated in to diketone moiety, showed good antioxidant property. It was also concluded that synthetic moiety containing pyrimidine, morpholine or piperidine ring imparts antioxidant activity. Hence the two series were designed and synthesized as antioxidant namely morpholino substituted styryl-phenyl pyrimidines and piperidinyl substituted styryl-phenyl pyrimidines. The reaction was of four steps. α,β unsaturated ketones were synthesized. Then synthesis of pyrimidine-2-thiols was carried out. Nucleophilic substitution reaction was carried out by using morpholine or piperidine followed by alkylation of the thiol group. Structure elucidation of the synthesized compounds was done by spectral analysis. The antioxidant activity of the synthesized compounds was determined by DPPH, Hydrogen peroxide, Super oxide and nitric oxide radical scavenging activity. Synthesized compounds exhibited highest activity against hydrogen radical in DPPH and Hydrogen peroxide radical scavenging activity. 3D QSAR was studied using SYBYL-X-1.2 and good correlation between physicochemical properties and biological activity for the inhibition of free radicals of the designed synthesized compounds was obtained. It can be concluded that there is a good correlationship between physicochemical parameters and the biological activity.