Pharmacology
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29939
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Browsing Pharmacology by Author "Acharya, Suchismita"
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Item Synthesis and Bioactivity of Nitric Oxide Donor and Antioxidant Drug Hybrid(2020) Nguyen, Ngoc; Weston, Courtney; Acharya, Suchismita; Khowaja, SanoberPurpose: In ischemic stroke or peripheral artery disease, there is a blockage of the arteries that results in increased free radicals and cell death. Our goal was to synthesize a hybrid compound SA-9-01 and assess the NO releasing and reactive oxygen species (ROS) scavenging ability using chemical assays. We hypothesize that the hybrid compound will prevent cell death by improving blood circulation and neutralizing ROS. Methods: SA-9-01 was synthesized using a synthetic procedure similar to a previously designed analog SA-2 and structure was verified by 1HNMR. The NO releasing activity was determined using the Griess assay by measuring the total nitrite formation. The xanthine oxidase assay was used to measure the ROS scavenging activity. Results: Compound SA-9 (25 mM) released NO at concentrations between 1.35-1.40 µM at t=90 mins sufficient to provide therapeutic activity, while a known NO donor SIN-1 released between 2-15 µM at same concentration and time point. From the xanthine oxidase assay, the scavenging ratio for SA-9-01 (250 µM) was about 20-25% at t=100 mins and comparable to previously described compound SA-2 and Baicalein (the positive control). Conclusion: Compound SA-9-01 was synthesized successfully with the correct chemical structure and was found to be a tautomer of the first batch SA-9. The Griess assay demonstrated that SA-9 releases physiological level of NO. SA-9-01 also demonstrated ROS scavenging activity. The testing of SA-9-01 in cells is under progress.Item Synthesis and Bioactivity Study of Novel Hybrid Antioxidant(2020) Weston, Courtney; Khowaja, Sanober; Acharya, Suchismita; Nguyen, NgocPurpose: Antioxidant enzymes are the first line defense for preventing oxidative stress (OS) by scavenging free radicals, and different enzymes scavenge different reactive oxygen species (ROS). We focused on two major antioxidants: superoxide dismutase (SOD), which removes superoxide; and glutathione peroxidase (GPx), which removes hydrogen peroxide radicals. The purpose was to synthesize a hybrid compound with multiple antioxidant activities and to test the total ROS scavenging ability using a chemical assay. The goal is to use this class of compound as a method of preventing and treating ophthalmologic diseases related to oxidative damage. Methods: Synthesis of a hybrid antioxidant MN-1-26 was carried out using an amide coupling reaction between 4-amino Tempol (a SOD mimetic) and NHBoc methionine followed by purification using liquid chromatography. Structure confirmation was done using proton NMR. The ROS scavenging chemical assay was conducted following a literature protocol where pyrogallol was used as the ROS generator. Changes in UV absorbance were measured at different time points to compare MN-1-26 (250µm) with SA-2 (a known SOD mimetic) and Baicalein (a polyphenolic antioxidant) as positive controls. Result: Compound MN-1-26 has the correct chemical structure, determined by proton NMR, with the highest superoxide scavenging ratio (28%) at 90 minutes compared to SOD mimetic SA-2 (22%), and Baicalein (24%). Conclusion: The hybrid antioxidant demonstrated superior ROS scavenging activity over individual antioxidants. Further cellular studies of MN-1-26 are under progress, with the goal of reducing OS and cell death in vitro.