Synthesis and anti-inflammatory effects evaluation of 1,3 substituted isatin derivatives

Abstract

Objectives: Inflammation is a pathophysiological response of the body to a variety of agents including infections and physical injury leading to local accumulation of plasma fluid and blood cells. Isatin as a promising heterocyclic molecule has shown interesting biological profile. In this study, some derivatives of isatin containing both Schiff and mannich base fragments were synthesized in a three-step procedure. Methods: Benzohydrazide derivatives were prepared by reaction of benzoat derivatives with hydrazine hydrate. The Schiff bases were formed by treatment isatin with the benzo hydrazide derivatives. The corresponding mannich bases have been synthesized by the reaction of the Schiff bases with amine derivatives in the presence of formaldehyde and trifluoroacetic acid. In the case of 2-hydroxybenzohydrazide, final product was synthesized by condensation the corresponding mannich base derivative with 2-hydroxybenzohydrazide. Final compounds were evaluated for anti-inflammatory activity using the croton oil-induced ear edema test. Results: Among tested compounds, compound b3 which included only mannich base fragment reduced inflammation very significantly. Compounds C2 and C3 containing both Schiff and mannich base groups showed moderate anti-inflammatory activity. Conclusion: It can be considered that the existence and nature of substituents at the 1 position of isatin nucleus play an important role in modulating their anti-inflammatory properties. © 2021, Faculty of Pharmaceutical Sciences, Chulalongkorn University. All rights reserved.