Bs Jayashree

Design and synthesis of 2-quinolones as antioxidants and antimicrobials: a rational approach

As an important class of compounds, 2-quinolones are isomeric to 4-quinolones and isosteric to coumarins. The compounds that have 2-quinolone moiety are associated with interesting biologic activities such as antibacterial, anticancer, antiviral, cardiotonic, and N-methyl-D-aspartate receptor inhibitor functions, among others. In the current study, based on the rational approach, lead molecules of the 2-quinolone skeleton were designed for binding to the bacterial DNA gyrase subunit A. Docking simulations and quantitative structure activity relationship (QSAR) analysis were performed using the Molegro Virtual Docker and Sarchitech softwares. Based on these studies, the 7-amino-4-methylquinolin-2(1H)-one parent compound and its carboxamides (JST 1–15) were synthesized using Conrad Limpach synthesis. The synthesized test compounds then were characterized by thin-layer chromatography and melting point determination, as well as by ultraviolet, infrared (IR), 1H-NMR, and MS studies. All synthesized and purified compounds were tested for antioxidant and antibacterial activity.

Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG) >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR) was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats.

Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin-resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin, creatinine and AGEs were decreased to near normal upon treatment with test compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma triglycerides, lipids, endogenous antioxidant defense and glycogen were restored in FD-fed rats after treatment with 3-hydroxyflavones. It is known that insulin resistance is partly because of oxidative stress and hence antioxidant activity was determined. They exhibited significant in vitro DPPH and ABTS radical scavenging activity (IC50: 10.66-66.63 µM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39–42.63 µM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 µM). All test compounds at concentrations 100-200 µM protected calf thymus DNA-damage by Fenton reaction. In addition, test compounds inhibited protein glycation in different in vitro antiglycation assays. JY-2 showed maximum potency in all the stages of glycation which was comparable to the standard quercetin and aminoguanidine. Test compounds also enhanced the glucose uptake by L6 myotubes at an EC50 much lower than that of quercetin. Thus the synthetic 3-hydroxyflavones were found to have good antidiabetic activity by pleotropic and multimodal suppression of insulin resistance and enhancement of glucose uptake by skeletal muscles. These compounds are non-toxic at the doses tested. Further, the combined antioxidant and antiglycation activities of these molecules have complementary benefits in management of diabetes.

Evaluation of the Antioxidant Activity of Novel Synthetic Chalcones and Flavonols

In the present study, newer chalcones and flavonols were synthesized by Algar-Flynn-Oyamada method, purified and characterized by spectral methods. The pure test compounds were evaluated for in vitro antioxidant activity using four models namely 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•), Nitric oxide (NO) and Lipid Peroxidation scavenging methods. This study indicate that, amongst the ten evaluated chalcones and flavones, five test compounds showed activity with IC50 value lesser than that of the standard ascorbic acid at 91.21 μM for 2,2-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging.