Microwave-Assisted Synthesis, in Silico Studies and in Vivo Evaluation for Antidiabetic Activity of New Brominated Pyrazoline Analogues

Abstract

Introduction: Pyrazolines have played crucial role in the drug discovery researches and have been used widely as an important pharmacophores or intermediet for synthesis of bioactive compounds. Objective: The aim of this work is to explore the potential of new brominated pyrazoline analogues as antidiabetic. Methods: Synthesis of brominated pyrazoline analogues have been conducted under microwave irradiation, in silico studies was performed using AutoDock 1.5.4 software packages and Nano scale MD Program 2.9, and the animal used in the in vivo evaluation is male albino mices (Mus musculus L.). Result: The in silico studies for antidiabetic activity showed that compound 3a is the most active compound and furthermore it can be developed as new active agents for antidiabetic. The in vivo evaluation showed that compound 3a have a good ability to increase the percentage of change in blood glucose level and weight loss prevention, decreasing of the drinking  water and also decreasing of the urine volume, significantly (p < 0.05) compared than negative control with dosage of 25, 50 and 100 mg/Kg of the body weight. Then, the oral administrations of compound 3a had no effect on damage that interferred the functional process of heart, liver and kidney of treated diabetic mices in the given dosages. Conclusion: This strategy reflects a logical progression for early stage drug discovery that can be used to successfuly identify drug candidates for antidiabetic agents.