Synthesis and Characterization of New 7-Chloroisatin Derivatives and Study of Their Potential Antioxidant Activity

Abstract

A series of novel spiro azetidine and thioazetidine scaffolds incorporating an isatin subunit were successfully synthesized. The protocol involved reacting Schiff base derivatives of 7-chloroisatin with phenyl isocyanate or phenyl thioisocyanate. The new derivatives were obtained in excellent yield and characterized by different techniques such as FTIR, HNMR and ¹³CNMR. Furthermore, in silico, in vitro, and in vivo investigations were performed to assess the bioactivity of prepared compounds as antioxidants. The in-silico analysis encompassed the evaluation of pharmacokinetic and pharmacodynamic properties for all compounds, revealing favorable characteristics. Subsequently, molecular docking studies were performed with two proteins: VEGFR-2 and ALR2. The results demonstrated good docking scores for compounds 1-4. The in vitro assessments involved the evaluation of the potential antioxidant activity of all compounds using two methods: the total antioxidant capacity method and the DPPH scavenging activity method. The results demonstrated that all compounds exhibited noteworthy to excellent antioxidant activity. Based on these findings, compound 2 was selected for further investigation in the in vivo study using rats. In the in vivo experiment, male rats were administered a dose of 200 mg/0.5ml DMSO/rat/ day of compound 2 for 4-weeks, and the concentrations of total antioxidant capacity and MDA in their serum were measured. The results indicated that compound 2 exhibited commendable performance as an antioxidant agent.