Development Of New Class Of Halogenated Chromones For The Treatment Of Alzheimers Disease

Abstract

The present study was aimed to evaluate the anti-Alzheimer s activity of newlinehalogenated chromones at different orientations. Based on molinspiration-drug newlinelikeness properties, halogenated chromones at different orientation were selected newlineand synthesized. The synthesized compound s structure was confirmed by IR, newlineMASS and NMR spectroscopy. All the synthesized compounds were tested for in newlinevitro acetylcholinesterase enzyme inhibitory activity. The result indicated that the newlinetest compound C1 possessed good neuroprotective activity when compared to the newlinestandard drug donepezil. Test compound C6 possessed least neuroprotective activity newlinecompared to standard and test drug C1. Acute toxicity studies were conducted in newlinemice by using OECD guidelines 420. The compound C1 and C6 was found that newline2000 mg/kg was safe dose. For in vivo study of the compound C1 and C6, 200 newlinemg/kg and 400 mg/kg doses were selected for testing anti-Alzheimer s disease newlineactivity as lower dose and higher dose respectively. In vivo studies were done for newlinebest active compound C1 (2-chloro flavone) and least active compound C6 (4-fluro) newlineby scopolamine (i.p.) and streptozocin (i.c.) induced learning and memory newlineimpairment in mice. The anti-Alzheimer s disease activity was studied using passive newlineavoidance test, elevated plus maze model, morris water maze and object recognition newlinetest, and it showed dose dependent increase in memory. The CNS effects were newlinestudied by using actophotometer and rotarod apparatus, there was no changes newlineobserved in the locomotor activity between all groups. After the studies, animals newlinewere sacrificed, blood and brain samples were collected. Biochemical parameters like newlinecholesterol, glucose levels in blood and oxidative stress markers such as SOD, newlineMDA, CAT, GPx, GSH and AchE in brain homogenate were measured. There is a newlinesignificant decrease in the serum blood glucose levels with test drug C1 and C6 with newlinescopolamine and STZ model.