Browsing by Author "Godugu, Kavitha"
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Item Fluorinated analog NMR s of organosulfur compounds from garlic (allium sativum): Synthesis, chemistry and anti-angiogenesis and antithrombotic studies(MDPI, 2017-11-24) Block, Eric; Bechand, Benjamin; Gundala, Sivaji; Vattekkatte, Abith; Wang, Kai; Mousa, Shaymaa S; Godugu, Kavitha; Mousa, Shaker A.; Yalçın, Murat; Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis activity of difluoroallicin (S-(2-fluoroallyl) 2-fluoroprop-2-ene-1-sulfinothioate) and S-2-fluoro-2-propenyl-l-cysteine, both easily prepared from commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of 1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2-dithiin, trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoroallyl)disulfane), and a bis(2-fluoroallyl)polysulfane mixture. All tested organosulfur compounds demonstrated effective inhibition of either FGF or VEG-mediated angiogenesis (anti-angiogenesis activity) in the chick chorioallantoic membrane (CAM) or the mouse Matrigel (R) models. No embryo mortality was observed. Difluoroallicin demonstrated greater inhibition (p < 0.01) versus organosulfur compounds tested. Difluoroallicin demonstrated dose-dependent inhibition of angiogenesis in the mouse Matrigel (R) model, with maximal inhibition at 0.01 mg/implant. Allicin and difluoroallicin showed an effective antiplatelet effect in suppressing platelet aggregation compared to other organosulfur compounds tested. In platelet/fibrin clotting (anti-coagulant activity), difluoroallicin showed concentration-dependent inhibition of clot strength compared to allicin and the other organosulfur compounds tested.Publication Lead-induced endothelial cell dysfunction: Protective effect of sulfated non-anticoagulant low molecular weight heparin(Korean Soc Environmental Risk Assessment & Health Science, 2021-04-12) Motawei, Shimaa M.; Sudha, Thangirala; Godugu, Kavitha; Mousa, Shaker A.; Yalçın, Murat; YALÇIN, MURAT; Bursa Uludağ Üniversitesi/Veteriner Fakültesi.; 0000-0002-5600-8162; AAG-6956-2021Objective The aim of this investigation is to determine the potential protective effect and mechanism of a novel non-anticoagulant heparin-derived product on lead (Pb) mediated endothelial cells (ECs) toxicity. Pb is known to have detrimental effects on human health by affecting the function of all systems of the human body due to its toxicity on ECs. Altered activities of the protective substances secreted by the vascular endothelium such as EC's tissue factor pathway inhibiter (TFPI), nitric oxide and other protective factors might increase the risk for vascular disorders. Heparin and its sulfated non-anticoagulant low molecular weight heparin (S-NACH) are known to enhance TFPI release from ECs, which is a protective mechanism for the ECs against thrombo-inflammation. Methods We examined 3-100 mu M Pb-induced dysfunction on ECs and the potential protective effect of 1-10 mu M S-NACH in returning the ECs' normal function. Methods included an in vitro tube formation assay and an in vivo Matrigel plug angiogenesis model in mice. Results We found that Pb-induced EC dysfunction by inhibiting EC viability. The cytotoxic effect of 3-100 mu M Pb on ECs inhibited angiogenesis in a dose-dependent manner. Pb disrupted ECs' normal physiological function by hindering the release of its endogenous vascular protective mediators TFPI-1 and TFPI-2. The impairment effect of 3-30 mu M Pb on ECs' release of both TFPIs was effectively reversed to normal levels by S-NACH in a concentration-dependent manner and combatted the harmful Pb effects on physiological angiogenesis. Conclusions Our data indicate that S-NACH, which is devoid of bleeding side effects, can effectively reverse potentially high-risk Pb-mediated endothelial cytotoxicity by reversing the physiological release of endogenous EC TFPIs.Item Pharmacokinetics, biodistribution, and anti-angiogenesis efficacy of diamino propane tetraiodothyroacetic acid-conjugated biodegradable polymeric nanoparticle(Nature, 2019-06-21) Li, Weikun; Bharali, Dhruba J.; Lin, Qishan; Godugu, Kavitha; Fujioka, Kazutoshi; Keating, Kelly A.; Mousa, Shaker A.; Yalçın, Murat; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734The anti-angiogenic agent, diamino propane tetraiodothyroacetic acid (DAT), is a thyro-integrin (integrin alpha v beta 3) antagonist anticancer agent that works via genetic and nongenetic actions. Tetraiodothyroacetic acid (tetrac) and DAT as thyroid hormone derivatives influence gene expression after they transport across cellular membranes. To restrict the action of DAT to the integrin alpha v beta 3 receptors on the cell surface, we used DAT-conjugated PLGA nanoparticles (NDAT) in an active targeting mode to bind to these receptors. Preparation and characterization of NDAT is described, and both in vitro and in vivo experiments were done to compare DAT to NDAT. Intracellular uptake and distribution of DAT and NDAT in U87 glioblastoma cells were evaluated using confocal microscopy and showed that DAT reached the nucleus, but NDAT was restricted from the nucleus. Pharmacokinetic studies using LC-MS/MS analysis in male C57BL/6 mice showed that administration of NDAT improved the area under the drug concentration curve AUC(()(0-)(48 h)) by 4-fold at a dose of 3 mg/kg when compared with DAT, and C-max of NDAT (4363 ng/mL) was 8-fold greater than that of DAT (548 ng/ mL). Biodistribution studies in the mice showed that the concentrations of NDAT were higher than DAT/Cremophor EL micelles in heart, lung, liver, spleen, and kidney. In another mouse model using female NCr nude homozygous mice with U87 xenografts, tumor growth was significantly decreased at doses of 1 and 3 mg/kg of NDAT. In the chick chorioallantoic membrane (CAM) assay used to measure angiogenesis, DAT (500 ng/CAM) resulted in 48% inhibition of angiogenesis levels. In comparison, NDAT at low dose (50 ng/CAM) showed 45% inhibition of angiogenesis levels. Our investigation of NDAT bridges the study of polymeric nanoparticles and anti-angiogenic agents and offers new insight for the rational design of anti-angiogenic agents.