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.
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.
Keywords
antioxidant
Azetidine
Isatin
molecular docking.