Design and Synthesis of an Aniline Derivative with Biological Activity on Heart Failure

2020 ◽  
Vol 23 ◽  
Author(s):  
Garcimarero-Espino E. Alejandra ◽  
Figueroa-Valverde Lauro ◽  
Rosas-Nexticapa Marcela ◽  
Lopez-Ramos Maria ◽  
Diaz Cedillo Francisco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Ischemia Reperfusion Injury ◽  
Simple Procedure ◽  
Low Cost ◽  
Ischemia Reperfusion ◽  
Aniline Derivative ◽  
Design And Synthesis ◽  
Aniline Derivatives ◽  
Injury Model

Background: Several compounds have been synthesized as a therapeutic alternative for heart failure; however, its preparation requires special conditions. Objective: The aim of this study, was to synthesize some aniline derivatives (4-9) from 3-ethynylaniline to evaluate their biological activity against heart failure. Methods: The synthesis of aniline derivatives involved a series of reactions such as etherification, addition, and cyclization. The structure of all compounds obtained was confirmed by spectroscopic and spectrometric methods. In addition, to evaluate the biological activity of compounds an ischemia/reperfusion injury model was used. Results: The results showed that compound 8 decreases heart failure, which translates into a decrease in the infarction area compared to compounds 4-7 and 9. Conclusion: This study is reported a facile method for the preparation of aniline derivatives. This method offers some advantages such as; a simple procedure, low cost, and ease of work. In addition, compound 8 showed an interesting biological activity against heart failure. This phenomenon is particularly interesting because the biological activity induced by this compound could involve a molecular mechanism different compared with other drugs used for the treatment of heart failure.

scholarly journals Activity Exerted by Fluoro-2,4-Dioxaspiro[Bicyclo[3.3.1]Indene Derivative Against Ischemia/Reperfusion Injury

2020 ◽  
Vol 9 (4) ◽  
pp. 1474-1484
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Thromboxane A2 ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Infarct Area ◽  
Cox 2

Several drugs for the treatment of heart failure; however, some of these drugs can produce some secondary effects such as arrhythmias and hypercalcemia and others. The aim of this investigation was to evaluate the biological activity of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure. The effect exerted of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure was evaluated in an ischemia/reperfusion model using indomethacin and ramatroban as a control. Furthermore, a theoretical study was carried out to determine the interaction of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative with COX-1, COX-2, and thromboxane A2 using the 5u6x, 3ntg, and 6iiu proteins as controls. The results showed that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative decrease the infarct and left ventricular pressure; however, this effect was inhibited in the presence of ramatroban. In addition, other data indicated that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative could interact with both COX-2 and thromboxane A2 protein surface. All these data indicate that the biological activity of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against infarct area and left ventricular pressure was via both COX-2 and thromboxane A2 inhibition. Therefore, this compound could be s candidate for the treatment of heart failure.

scholarly journals Biological Activity Exerted by Crocodylus moreletii Oil Against Heart Failure using an Ischemia/Reperfusion Model

2020 ◽  
Vol 9 (3) ◽  
pp. 1284-1293
Keyword(s):  
Heart Failure ◽  
Fatty Acids ◽  
Biological Activity ◽  
Sodium Oleate ◽  
Perfusion Pressure ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Biological Evaluation ◽  
Infarct Area ◽  
Crocodylus Moreletii

Several bioactive substances have been isolated from some crocodiles for therapeutic purposes; however, there is scarce information on the biological activity of Crocodylus moreletii against heart failure. The aim of this investigation was to evaluate the biological activity of Crocodylus moreletii oil against either heart failure and perfusion pressure. Fatty acids involved in the Crocodylus moreletii oil was determinate by gas chromatography analysis. In addition, the effect exerted by Crocodylus moreletii oil against heart failure (translated as infarct area) was evaluated using either sodium oleate or methyl linolelaidate as controls in an ischemia-reperfusion injury model. In addition, the biological activity of either Crocodylus moreletii (Duméril & Bibron, 1851) oil or sodium oleate or methyl linolelaidate on perfusion pressure was evaluated using an isolated rat heart model. The results showed a high concentration of linolelaidate (23.3%) and oleate (20.3%) fatty acids in the sample from Crocodylus moreletii. Also, the results of biological evaluation shown that both Crocodylus moreletii oil and sodium oleate decreased the infarct area through increase either perfusion pressure and resistance coronary compared with methyl linolelaidate. In conclusion, the results suggest that both Crocodylus moreletii oil and sodium oleate can exert changes on perfusion pressure and coronary resistance translated as a decrease of infarct area and consequently bring a cardioprotective effect.

scholarly journals New chloroamide-steroid derivative with biological activity on a casein kinase 2 (CK2)

2020 ◽  
Vol 10 (2) ◽  
pp. 5145-5155
Keyword(s):  
Biological Activity ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Facile Synthesis ◽  
Infarct Area ◽  
Injury Model ◽  
Steroid Derivative

Several casein kinase 2 inhibitors have been prepared using some protocols which require dangerous reagents and specific conditions. The aim of this study was to synthesize a new chloroacetamide-steroid derivative using some chemical tools. In addition, the effect exerted by chloroacetamide-steroid derivative on casein kinase 2 (CK2) was determinate in an ischemia-reperfusion injury model using quinalizarin and N-tertbuthyl-2-chloroacetamide as controls. The results showed that 1) the chloroacetamide-steroid derivative significantly decrease the ischemia-reperfusion injury translated as infarct area compared with quinalizarin and N-tertbuthyl-2-chloroacetamide. In conclusion, in this study, is reported a facile synthesis of a new chloroacetamide-steroid derivative with biological activity against CK2.

scholarly journals Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chong Huang ◽  
Yan Chen ◽  
Bin Lai ◽  
Yan-Xia Chen ◽  
Cheng-Yun Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Akt Pathway ◽  
Acute Renal Injury ◽  
Injury Model ◽  
Renal Ischemia Reperfusion Injury

Abstract Background Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.

scholarly journals Comparison of the protective effects of desflurane and propofol anesthesia in rats: a hepatic ischemia-reperfusion injury model

2013 ◽  
Vol 43 ◽  
pp. 592-598
Author(s):  
Ayca TAŞ TUNA ◽  
Cengiz Bekir DEMİREL ◽  
Yusuf ÜNAL ◽  
Aslıhan ÇAVUNT BAYRAKTAR ◽  
Demet YILMAZER ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Hepatic Ischemia ◽  
Injury Model ◽  
Hepatic Ischemia Reperfusion

Abstract 428: Pharmacologic and Activated Fibroblast-specific Gβγ-GRK2 Inhibition is Protective Following Ischemia Reperfusion Injury

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Joshua G Travers ◽  
Fadia A Kamal ◽  
Michelle L Nieman ◽  
Michelle A Sargent ◽  
Jeffery D Molkentin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Reperfusion Injury ◽  
G Protein ◽  
Knockout Mice ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Ventricular Compliance

Heart failure is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Cardiac fibroblasts are responsible for extracellular matrix homeostasis, however upon injury or pathologic stimulation, these cells transform to a myofibroblast phenotype and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation induces excess signaling through G protein βγ subunits and ultimately the pathologic activation of G protein-coupled receptor kinase 2 (GRK2). We hypothesized that Gβγ-GRK2 inhibition plays an important role in the cardiac fibroblast to attenuate pathologic myofibroblast activation and cardiac remodeling. To investigate this hypothesis, mice were subjected to ischemia/reperfusion (I/R) injury and treated with the small molecule Gβγ-GRK2 inhibitor gallein. While animals receiving vehicle demonstrated a reduction in overall cardiac function as measured by echocardiography, mice treated with gallein exhibited nearly complete preservation of cardiac function and reduced fibrotic scar formation. We next sought to establish the cell specificity of this compound by treating inducible cardiomyocyte- and activated fibroblast-specific GRK2 knockout mice post-I/R. Although we observed modest restoration in cardiac function in cardiomyocyte-specific GRK2 null mice, treatment of these mice with gallein resulted in further protection against myocardial dysfunction following injury, suggesting a functional role in other cardiac cell types, including fibroblasts. Activated fibroblast-specific GRK2 knockout mice were also subjected to ischemia/reperfusion injury; these animals displayed preserved myocardial function and reduced collagen deposition compared to littermate controls following injury. Furthermore, systemic Gβγ-GRK2 inhibition by gallein did not appear to confer further protection over activated fibroblast-specific GRK2 ablation alone. In summary, these findings suggest a potential therapeutic role for Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, interstitial fibrosis and heart failure progression.

Abstract 14834: Protective Role of Cardiomyocyte-derived Ddt in Ischemic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yina Ma ◽  
Xiaoyue Hu ◽  
Daniel Pfau ◽  
Xiaohong Wu ◽  
Veena Rao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Map Kinase ◽  
Ischemic Cardiomyopathy ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
P38 Map Kinase ◽  
Lv Function ◽  
Acute Ischemia ◽  
S6 Kinase ◽  
Sham Surgery

Background: D-dopachrome tautomerase (DDT), the only homolog of macrophage migration inhibitory factor (MIF), is a cytokine highly expressed in cardiomyocytes and exerts autocrine-paracrine effects by signaling through the CD74 receptor. Endogenous DDT and MIF prevent acute ischemia-reperfusion injury and pressure overload-induced heart failure in mice. This study investigated whether endogenous cardiomyocyte DDT has a role in ischemic cardiomyopathy (ICM). Methods: LV tissue was obtained from patients with ICM during heart transplantation and from non-transplanted donor hearts. Plasma DDT concentrations were measured in heart failure outpatients with ICM. Cardiomyocyte-specific DDT knockout (cKO) and littermate control (CON) mice underwent MI or sham surgery. Serial echocardiography was performed to assess LV remodeling after MI or sham surgery. Tissue from the non-infarct region was analyzed 3 days and 4 weeks after MI or sham surgery for histology and molecular studies. Results: Cardiac DDT mRNA and protein expression were reduced in LV from patients transplanted for ICM (n=8). Plasma DDT concentrations below the median value were associated with worse survival in ICM outpatients (p<0.05, n=32). In mice, baseline LV function was similar in DDT cKO and CON after sham surgery and 3 days post-MI. However, DDT cKO mice developed more rapid LV dilatation and decreased LV ejection fraction and stroke volume as early as 1-week post-MI (n=4-6/group, all P<0.05). The DDT cKO mice had smaller cardiomyocyte cross-sectional area 4 weeks after MI (p <0.05), as well as early diminished phosphorylation of mTOR and S6-kinase (3 days post-MI). They also showed increased apoptosis 3 days post-MI and an early increase in p38 MAP kinase activation. Conclusion: Cardiomyocyte-derived DDT prevents adverse cardiac remodeling in ICM, potentially through modulating mTOR/S6 kinase (adaptive hypertrophy) and p38 MAP kinase (limiting apoptosis). Down-regulation of DDT in patients with ICM may contribute to the pathogenesis of advanced heart failure.

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