Sanju, K (2016) Quinolin-2-One Analogs: In Silico Design, Synthesis, in Vitro Antioxidant, in Vivo Anti-Inflammatory, Analgesic and Ulcerogenic Potential Studies. Masters thesis, KMCH College of Pharmacy, Coimbatore.
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Abstract
AIM AND OBJECTIVES:Inflammation is a universal host defence process involving a complex network of cell-cell mediator and tissue interactions. Inflammatory diseases cover a broad spectrum of conditions including autoimmune diseases (eg:rheumatoid arthritis),osteoarthritis, inflammatory bowel disease, multiple sclerosis, asthma, chronic obstructive pulmonary disease, allergic rhinitis, infectious diseases, various types of cancers and cardiovascular diseases. Until a few years ago, inflammatory disorders were treated primarily with relatively non selective anti- inflammatory drugs such as such as corticosteroids and various NSAIDs , however, now a days several mediator antagonists alone or in combination and gene therapy are also bring tried. Research in last few decades has shown that inflammation is regulated by a large number of pro and anti-inflammatory mediators. Advent of genomic era has emphasised the role of altered gene expression as fundamental to aetiology of inflammation and immune disorders..Efforts to develop new safer and more effective anti-inflammatory drugs are based on the role of key mediators identified as the key culprits in this condition. Inhibitors which specifically interfere with different components of different intracellular signalling pathways or inhibit the activation of transcription factors responsible for the expression of disease related genes have applications as novel therapeutic agents in inflammation. Inorder to search newer inhibitors of inflammatory signals, several chemical entities are being cloned with the help of in silico drug design stratergies. Quinolinones are the conventional scaffolds with antibacterial activity.As an important class of compounds, quinolin-2-ones 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. This study aimed to design, synthesis and evaluate various quinolin-2-one analogs, which contain thiazole, oxazole, aminopyridine, methyl piperazine and phenylpiperazine substitutions. The study also targeted in designing a molecule which is a selective COX2 inhibitor and thus can overcome the side effects caused by existing NSAIDs. The study focuses on designing compounds with quinolin-2-one nucleus as potent COX-2 inhibitor and thereby evaluating in vitro antioxidant and in vivo anti-inflammatory and analgesic activity followed by evaluating the ulcerogenic potential of the compounds. RESULT AND DISCUSSION: In vitro antioxidant activity:Free radicals are key signalling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils at the site of inflammation causes endothelial dysfunction and tissue injury. These reactive radicals and oxidants may injure cells and tissue directly via oxidative degradation of essential cellular components as well as injure cells indirectly by altering the protease/antiprotease balance that normally exist within the tissue interstitium. The Reactive oxygen metabolites may also initiate and/or amplify inflammation via the up regulation of several genes involved in the inflammatory response such as those code for pro inflammatory cytokines and adhesion molecules. Thus maintaining adequate anti-oxidant status may provide an useful approach in attenuating inflammation. Previous studies suggest that the compounds with quinolin-2-one nucleus posess remarkable anti-oxidant activity.Also,the anti-oxidant potential evaluation is inevitable as quinolin-2-one is isosteric to coumarins, which are well known for its anti-oxidant property. The anti-oxidant activity of all the synthesised compounds was evaluated by using DPPH and ABTS assay. The IC50 values were calculated using Graphpad prism5 software and compared with that of ascorbic acid and quercetin.TheIC50 value is defined as the concentration of antioxidant required for 50% scavenging of radicals and lower IC50 value corresponds to a higher antioxidant activity. The antioxidant activity of the compound was measured in terms of hydrogen donating or radical scavenging ability, using the DPPH method. The mechanism of ABTS assay is based upon the electron donating radical scavenging reaction by antioxidants which prevent the formation of coloured ABTS radical. The IC50 values of the synthesised compounds were compared with that of ascorbic acid and quercetin.The in vitro anti-oxidant activity of synthesised compounds in ABTS and DPPH radical scavenging assay as tabulated in Table 7.2 and Table 7.4. The results demonstrate that the tested compounds serve as free radical scavenger/inhibitor, acting possibly as primary antioxidants
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Quinolin-2-One Analogs; Silico Design ; Antioxidant ; Vivo Anti-Inflammatory ; Analgesic ; Ulcerogenic Potential Studies |
| Subjects: | PHARMACY > Pharmacology |
| Depositing User: | Ravindran C |
| Date Deposited: | 05 Jan 2018 05:48 |
| Last Modified: | 05 Jan 2018 08:14 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/4963 |
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