Synthesis, Analytical Characterization and Anti-Diabetic Activity of Some Heterocycles of Quinazolin-4(3H)one

Abstract

Aim: Novel quinazolin-4(3H)-one heterocycles were synthesized and assessed for their anti-diabetic activity. Non-enzymatic glycosylation of haemoglobin assay was carried out to identify their potential as anti-diabetic. The cyclization of quinazolinone-4(3H)-one heterocycles was achieved, whereas carbon-carbon cross coupling reactions were carried out using Sonogashira and Suzuki-Miyaura reaction conditions and characterized with analysis. This synthesis method afforded corresponding 2, 3 and 6 substituted quinazolin-4(3H)-ones (3a to 3m) with excellent yields. Methods: 2-Amino-6-bromobenzoic acid was used as a substrate which was converted to corresponding benzamide derivatives (1a-1b)  by reaction with benzylamine or cyclohexylamine using acid-amine reaction, followed by cyclization and oxidation using suitable aldehyde in DMSO under microwave condition to give bromo substituted quinazolin-4(3H)-ones (2a-2c), which were cross coupled to suitable terminal alkyne with palladium catalyst as well as copper co-catalyst using Sonogashira condition to obtain desired (3a-3h) and suitable boronic acid with palladium catalyst using Suzuki-Miyaura condition to obtain desired (3i-3m). All synthesized compounds were characterized by FTIR, proton NMR, LC-MS analysis and evaluated for in vitro anti-diabetic activity using non-enzymatic glycosylation of haemoglobin assay. Results: Compounds 3m showed good inhibition of glycosylation of haemoglobin which in turn suggest good anti-oxidant potential on metabolism of glucose and hence lower glucose concentration. It showed IC50 value of 35.91±0.82 µg/mL which was comparable to the standard alpha tocopherol (34.47±0.87µg/mL). Conclusion: In-vitro non-enzymatic glycosylation of haemoglobin method is one of important assays to judge the control of diabetes. The haemoglobin present in RBCs has an affinity to bind with glucose. The greater the glucose level in blood, more amount of glucose-bound (called glycosylated) haemoglobin will be formed. Accordingly, presence of lower concentration of glycosylated haemoglobin is a sure guide to the lower concentration of glucose in the blood. Synthesized compounds (3a-3m) lower the blood glucose level and 3m has highest potential among those which can be further developed as potent anti-diabetic.