Molecular Docking, Synthesis and In vitro Alpha Amylase Activities of Newer Generation Imidazolo-Pyrimidine Derivatives

A set of newer generation imidazolo-pyrimidine derivatives was designed, synthesized, and evaluated for in-vitro alpha amylase activity. The design of the molecules was fully depend upon the structural features of previously developed molecules, and then all the molecules were docked with ۱OSE porcine alpha amylase enzyme which showed good docking interaction scores between (-۹.۲ and -۱۰.۲) kcal/mol compared to standard acarbose (-۶.۹ kcal/mol). The interacting residues of (F۱-F۶) and ۱OSE showed similar amino acid lining as present in the active site. The synthetic procedure of the molecules (F۱-F۶) was divided into three parts such as synthesis of chalcone derivative using aromatic aldehyde and acetophenone, synthesis of phenyl linked oxazolone derivatives using aromatic aldehyde and hippuric acid, then finally merged both the final products of step ۱ and step ۲ in presence of glacial acetic acid to obtain the final series of molecules. All the molecules showed characteristic peaks in FTIR, ۱H-NMR, and Mass spectrometry with sharp melting point and single peak in TLC plate. Then in vitro alpha amylase inhibition activity was performed which showed that all the molecules observed with good IC۵۰ values than standard acarbose. The presence of hydroxyl and methoxy group showed good impact on biological activity. Finally the results postulated that F۳ was the best molecule as in vitro alpha amylase inhibitor.

Keywords:

Diabetes Mellitus , Imidazolo-Pyrimidine , Molecular docking , Synthesis , Alpha Amylase