Development of novel, green, efficient approach for the synthesis of indazole and its derivatives; insights into their pharmacological and molecular docking studies

Abstract

Indazole is a potent heterocycle with wide range of biological applications. It is less naturally available alkaloid widely used in traditional medicine for the treatment of allergies, blood pressure, etc. In recent years due to the utility of indazoles as pharmacophores in drug discovery, it has been exemplified in recent research. The existing method of synthesis involves carbon-nitrogen bond formation using ccopper, costly Pd metal catalyst i.e.; Buchwald Hartwig coupling. Since it is the need of hour for simple method, we, report a new efficient and economically feasible, user friendly synthesis of indazoles by utilizing less hazardous raw materials, eliminating use of metal catalyst therefore coming up with a greener method. The sequence involves carbon-nitrogen bond formation via simple ipso substitution, by replacing copper and costly Pd, catalyst. This new green synthetic procedure includes two steps synthesis of 1H-indazole derivatives involving arylhydrazones as an intermediate. Further in order to better understand the biological significance of the novel Indazole and its derivatives, Molecular docking studies for antifungal activity were carried out against lanosterol 14 alpha-demethylase for all the newly synthesized molecules with reference to the standard drug fluconazole, in line with above docking studies the in-vitro anti-microbial, anti-oxidant and anti-inflammatory activity were conducted among which our synthesized moieties showed excellent results for antifungal activity. Thus, we report an efficient, eco-friendly strong synthetic method for the synthesis of novel Indazole and its derivatives.