Abstract
Background: Imidazolones as well as Schiff base are extensively used as building blocks for the synthesis of various pharmaceutically active agents. The use of synthetic antioxidant for use in the diet and therapy demands a great deal of research attention for synthetic antioxidants. It was observed that the π-excessive ring systems are responsible for antioxidant activity of the compounds.
Objective: The primary objective of this study was to develop a new method to synthesize imidazalone derivatives which are evaluated for in vitro antioxidant activity in order to check their nutraceutical value.
Methods: Novel method for the synthesis of imidazalone derivatives is developed starting from simple easily accessible glycine, thiophene aldehyde and benzoyl chloride. The synthesis of target molecules is achieved in four steps via formation of an intermediate oxazolone which undergoes ring opening on reaction with hydrazine hydrate and subsequent cyclization with aldehydes in presence of acid catalyst.
Results: All Imidazolone compounds were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Almost all the tested imidazalone compounds showed moderate to excellent activity, the substitution on arylidene group substantially influenced their overall activity. The compound 3-{[(E)-(4-chlorophenyl)methylidene]amino}-2- phenyl-5- (thiophen-2-ylmethylidene)-3,5-dihydro-4H-imidazol-4-one (9) showed very high radical scavenging capacity with IC50 value 2.886 µg/ml in comparison with the standard ascorbic acid (1.439 µg/ml). The antioxidant activities of the synthesized compounds appeared in the following order 6 >5> 13> 8>7>20>11>12>10>19>15>14>18>16 and 17. Further in silico studies complement the in vitro antioxidant studies.
Conclusion: Compound, 3-{(4-chlorophenyl)methylidene]amino}-2-phenyl-5-(thiophen-2-ylmethylidene)- 3,5-dihydro-4H-imidazol-4-one (9) displayed best antioxidant activity due to the presence of active chloro group. Compounds bearing hydroxyl group at para and ortho position (16 and 18) showed very low activity. This anomalous result could be explained on the basis of intramolecular hydrogen bonding. These results were complement the in silico antioxidant studies.
Keywords: Imidazolone, schiff base, antioxidant, structure-activity, molecular docking, glycine.
Graphical Abstract
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