ABSTRACT
We investigated the prognostic implications of the systemic immune-inflammatory index (SII), atherogenic index of plasma (AIP), C-reactive protein/albumin ratio (CAR), neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and triglyceride/glucose index (TGI) in the MORtality predictors in the CORonary Care Units in TURKey (MORCOR-TURK) population. This is the largest registry of coronary care unit (CCU) patients in Turkey (3157 patients admitted to CCU in 50 different centers). The study population was divided into two according to in-hospital survival status; 137 patients (4.3%) died in-hospital follow-up. A significant correlation was found between death and SII, CAR, NLR, and PNI but not for AIP and TGI in logistic regression. In Model 1 (combining parameters proven to be risk predictors), the -2 log-likelihood ratio was 888.439, Nagelkerke R2 was 0.235, and AUC (area under curve) was 0.814 (95% CI: 0.771-0.858). All other models were constructed by adding each inflammatory marker separately to Model 1. Only Model 3 (CAR + Model 1) had a significantly greater AUC than Model 1 (DeLong P = .01). Our study showed that CAR, but not other inflammatory index, is a significant predictor of in-hospital mortality in CCU patients when added to proven risk predictors.
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Acute coronary syndrome and pulmonary embolism (PE) are clinical entities sharing similar presentation and risk factors. Risk scores and indexes help to identify disease severity in both diseases. In this study, we aimed to evaluate if the Global Registry of Acute Coronary Events (GRACE) risk score could predict 30-day mortality and the need for thrombolytic treatment in patients with acute PE. Patients hospitalized with a diagnosis of PE in our tertiary center between January 2018 and May 2022 were included in this retrospective study. Pulmonary Embolism Severity Index (PESI) and GRACE risk scores on admission were calculated using clinical, electrocardiographic, and laboratory parameters for each patient. A total of 197 patients were included. The 30-day mortality rate was 28.4% whereas 32.5% of the patients required thrombolytic treatment. GRACE and PESI scores were found independent risk factors associated with 30-day mortality and the need for thrombolytic treatment. A cut-off value of 160.5 for GRACE score was associated with 88.5% sensitivity and 89.4% specificity in prediction of 30-day mortality. In contrast, GRACE score had 61.0% sensitivity and 60.0% specificity in the prediction of the need for thrombolytic treatment when the cut-off value was 147. In conclusion, GRACE risk score has an effective discriminating power in determining the early mortality of patients with acute PE. The incidence of short-term PE-related mortality was significantly increased in patients with high GRACE risk scores. Concomitant use of GRACE and PESI risk scores may aid in defining patients with high-risk PE and help predict poor prognosis with high specificity and probability.
Subject(s)
Pulmonary Embolism , Humans , Risk Assessment , Retrospective Studies , Prognosis , Risk Factors , Pulmonary Embolism/complications , Fibrinolytic Agents/therapeutic use , Registries , Severity of Illness Index , Acute DiseaseABSTRACT
OBJECTIVE: Transcatheter aortic valve implantation (TAVI) may ameliorate renal function and increase blood pressure (BP). We aimed to investigate the association between increased BP and improved renal function (IRF) after TAVI. METHODS: A total of 176 patients who had undergone TAVI were evaluated retrospectively. BP records that were taken 24 h before and 72 h after TAVI were reviewed. Pre-procedural, post-procedural 48 h, and the first month estimated glomerular filtration rate (eGFR) levels were noted. IRF was accepted as aâ ≥â 10% increase in eGFR. The predictors of acute kidney injury (AKI) development at 48 h and IRF at 1 month were investigated. The association between mortality and BP response was assessed. RESULTS: A total of 157 patients were included in this study after exclusion as defined in the methodology. Mean age was 78.1â ±â 7,1 and 51.6% were female. AKI occurred in 25.5% of patients and baseline eGFR and male gender were found as independent predictors for AKI development. IRF was observed in 16% at 48â h and 31.8% of patients at 1-month follow-up. Positive BP response was seen in 42% of patients. Pre-procedural chronic kidney disease, positive BP response, and an early increase in eGFR emerged as independent predictors of IRF at the first month. The patients with positive BP response were found to have decreased mortality at 710 days follow-up. CONCLUSION: Positive BP response after TAVI is related to improved survival and renal functions. The beneficial effect of TAVI on renal function may be precisely evaluated at 1st month rather than 48â h.
Subject(s)
Acute Kidney Injury , Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Male , Female , Transcatheter Aortic Valve Replacement/adverse effects , Retrospective Studies , Blood Pressure , Risk Factors , Aortic Valve Stenosis/surgery , Kidney , Treatment OutcomeABSTRACT
Objectives: Hemogram parameters such as mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLr), red cell distribution width and platelet distribution width are widely used inflammatory indicators to assess prognosis in various cardiovascular diseases. In this study, we aimed to investigate the role of hemogram parameters to predict the development of contrast-induced nephropathy (CIN) in patients presenting with non-ST segment elevation myocardial infarction (non-STEMI) and treated with percutaneous coronary intervention (PCI). Methods: All pateints who underwent PCI with a diagnosis of non-STEMI between 2017 and 2020 in our center were included retrospectively in this study. Results: A total of 387 patients were included in this retrospective study. Advanced age (p=0.001, ß:0.005, OR [95â¯% CI]: 0.002-0.007), diabetes mellitus (p=0.013, ß:0.205, OR [95â¯% CI]: 0.150-0.260), congestive heart failure (p=0.009, ß:0.095, OR [95â¯% CI]: 0.024-0.166), volume of contrast medium (p=0.008, ß:0.241, OR [95â¯% CI]: 0.184-0.392), MPV (p=0.02, ß:0.047, OR [95â¯% CI]: 0.028-0.065) and NLr (p=0.001, ß:0.052, OR [95â¯% CI]: 0.040-0.063) were found as independent risk factors associated with CIN development according to multivariate logistic regression analysis. A cut off value of 5.5 for NLr was associated with 79.6â¯% sensitivity and 79.5â¯% specificity and 9.05 for MPV was associated with 64.1â¯% sensitivity and 58.7â¯% specificity in prediction of CIN development. Conclusions: Hematological parameters, assessed by routine blood count analysis may serve as a promising and useful marker for CIN especially when used in combination with traditional risk factors. MPV and NLr were demonstrated as predictors of CIN development in non-STEMI patients who were treated with PCI in our study.
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Aortic valve stenosis (AS) is the most common valvular disease, and surgical or transcatheter aortic valve replacement (TAVR) are the treatment options. Diminish in platelet production or dysfunction may occur due to shear stress, advanced age, and other coexisting diseases in AS patients. Bleeding is one of the complications of TAVR and associated with increased mortality. MPV (mean platelet volume) indicates platelet's thrombogenic activity. Overproduction or consumption of platelets in various cardiac conditions may affect MPV values. We aimed to investigate the pre and postprocedure MPV percentage change (MPV-PC) and its association with post-TAVR short-term complications. A total of 204 patients who underwent TAVR with a diagnosis of severe symptomatic AS were included. The mean age was 78.66â±â6.45 years, and 49.5% of patients were women. Two groups generated according to composite end point (CEP) development: CEP(+) and CEP(-).110 patients(53.9%) formed CEP(+) group. Although baseline MPV and platelet levels were similar between groups, MPV was increased ( P â<â0.001) and platelet was decreased ( P â<â0.001) significantly following the procedure when compared to baseline. MPV-PC was significantly higher in the VARC type 2-4 bleeding ( P â = â0.036) and major vascular, access-related, or cardiac structural complication groups ( P â = â0.048) when CEP subgroups were analyzed individually. Regression analysis revealed that diabetes mellitus [ P â = â0.044, ß: 1.806 odds ratio (95% confidence interval): 1.016-3.21] and MPV-PC [ P â = â0.007,ß: 1.044 odds ratio (95% confidence interval): 1.012-1.077] as independent predictors of CEP development at 1 month after TAVR. The MPV increase following TAVR may be an indicator of adverse outcomes following TAVR procedure within 1-month.
Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Female , Aged , Aged, 80 and over , Male , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Mean Platelet Volume , Treatment Outcome , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnosis , Risk Factors , Aortic Valve/surgeryABSTRACT
BACKGROUND: Liver is one of the target organs in patients with symptomatic severe aortic stenosis and reduced ejection fraction. We aimed to evaluate the prognostic impact of liver function reserve as assessed by albumin-bilirubin score on 30-day and 1-year mortality and rehospitalization at 1 year in patients with severe symptomatic aortic stenosis and reduced ejection fraction undergoing transcatheter aortic valve implantation. METHODS: The patients with severe symptomatic aortic stenosis and reduced ejection fraction who were hospitalized between 2013 and 2021 were included in this single-center retrospective study. Preoperative bilirubin and albumin levels were used for albumin-bilirubin score calculation as in the original report. The total primary outcomes were deï¬ned as 30-day and 1-year all-cause mortality and hospitalization for decompensated heart failure within 1 year. Two groups were generated based on albumin-bilirubin score scores: high (>-2.25) and low (≤-2.25) albumin-bilirubin score groups. RESULTS: A total of 77 patients (49 male) were included in the study. and 29 (37.7%) patients died within 1 year of follow-up with 17 corresponding to 30-day mortality. There was no diï¬erence between high and low albumin-bilirubin score groups in terms of length of hospital stay, postprocedural complications, and re-hospitalization within 1 year, while 30-day mortality (50.0% vs. 4.3%, P < 0.0001) and 1-year mortality (80.0% vs. 10.6%, P < 0.0001) were signiï¬cantly higher in the high albumin-bilirubin score group. Hence, total primary outcomes (86.7% vs. 44.7%, P < 0.0001) were signiï¬cantly higher in the high albumin-bilirubin score group. CONCLUSION: High albumin-bilirubin score (> -2.25) was found as an independent risk factor associated with 30-day and 1-year mortality and total primary outcomes. The results of this study suggest that preprocedural assessment of the albumin-bilirubin score gives additional information to stratify of patients with severe symptomatic aortic stenosis with reduced ejection fraction.
Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Ventricular Dysfunction, Left , Humans , Male , Stroke Volume , Ventricular Function, Left , Aortic Valve Stenosis/complications , Retrospective Studies , Treatment Outcome , Risk Factors , Albumins , Aortic Valve/surgeryABSTRACT
INTRODUCTION: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) are validated scoring systems for short-term risk estimation after coronary artery bypass grafting (CABG). The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score is originally aimed to estimate mortality in heart failure patients; however, it has showed a similar power to predict mortality after heart valve surgery. In this study, we sought to evaluate whether MAGGIC score may predict short and long-term mortality after CABG and to compare its power with EuroSCORE II and STS scoring systems. METHODS: Patients who underwent CABG due to chronic coronary syndrome at our institution were included in this retrospective study. Follow-up data were used to define the predictive ability of MAGGIC and to compare it with STS and EuroSCORE-II for early, one-year, and up to 10-year mortality. RESULTS: MAGGIC, STS, and EuroSCORE-II scores had good prognostic power, moreover MAGGIC was better for predicting 30-day (area under the curve [AUC]: 0.903; 95% confidence interval [CI]: 0.871-0.935), one-year (AUC: 0.931; 95% CI: 0.907-0.955), and 10-year (AUC: 0.923; 95% CI: 0.893-0.954) mortality. MAGGIC was found to be an independent predictor to sustain statistically significant association with mortality in follow-up. CONCLUSION: MAGGIC scoring system had a good predictive accuracy for early and long-term mortality in patients undergoing CABG when compared to EuroSCORE-II and STS scores. It requires limited variables for calculation and still yields better prognostic power in determining 30-day, one-year, and up to 10-year mortality.
Subject(s)
Coronary Artery Bypass , Heart Failure , Humans , Aortic Valve/surgery , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
Eight new hybrid constructs containing a series of sulfonamide and 1,2,3-triazole units were designed and synthesized. Anticancer, antioxidant and cholinesterase activities of these hybrid structures were investigated. In our design, the Cu(I)-catalyzed click reaction between N,4-dimethyl-N-(prop-2-yn-1-yl)benzenesulfonamide (6) and aryl azides 8a-h was used. Antioxidant activity values of 9f (IC50: 229.46 ± 0.001 µg/mL) and 9h (IC50: 254.32 ± 0.002 µg/mL) hybrid structures were higher than BHT (IC50: 286.04 ± 0.003 µg/mL) and lower than Ascorbic acid (IC50: 63.53 ± 0.001 µg/mL) and α-Tocopherol (IC50: 203.21 ± 0.002 µg/mL). We determined that the cytotoxic effects of hybrid constructs 9d (IC50: 3.81 ± 0.1084 µM) and 9g (IC50: 4.317 ± 0.0367 µM) against A549 and healthy cell line (HDF) are much better than standard cisplatin (IC50: 6.202 ± 0.0705 µM). It was determined that the AChE inhibitory activities of all synthesized compounds were much better than Galantamine used as a standard. In particular, 9c (IC50: 13.81 ± 0.0026 mM) had ten times better activity than the standard Galantamine (IC50: 136 ± 0.008 mM). The ADMET properties of the molecules have been thoroughly examined and met the criteria for drug-like substances. They also have a high oral absorption rate, as they can effectively cross the blood-brain barrier and are easily absorbed in the gastrointestinal tract. In vitro experiments were confirmed by in silico molecular docking studies.Communicated by Ramaswamy H. Sarma.
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INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have been shown to reduce the risk of atrial fibrillation (AF) occurrence in patients with diabetes mellitus (DM). In this prospective study, we aimed to analyze the effect of SGLT-2 inhibitors as an add-on therapy to metformin on P wave indices and atrial electromechanics in patients with type 2 DM. METHODS: A total of 144 patients enrolled. Electrocardiographic indices were recorded on admission and at 3rd and 6th month of the combination therapy. P wave indices and atrial electromechanical coupling intervals were measured and compared. RESULTS: Although decrease in P wave dispersion (62.78 ± 9.59 vs. 53.62 ± 10.65; p = .002) became significant at 6th month of combination therapy, significant decreases in P wave terminal force in V1 (37.79 ± 3.45 vs. 32.01 ± 5.74; p = .035), left atrial volume index (35.87 ± 6.57 vs. 31.33 ± 7.31; p = .042), left sided intra-atrial electromechanical delay (32.09 ± 9.17 vs. 27.61 ± 8.50; p = .016), right sided intra-atrial electromechanical delay (31.82 ± 4.92 vs. 27.65 ± 8.05; p = .042), and interatrial electromechanical delay (29.65 ± 7.52 vs. 25.96 ± 4.30; p = .044) were seen as early as 3rd month of treatment. Besides, there was no statistically significant difference between Empagliflozin and Dapagliflozin subgroups in terms of mentioned parameters. CONCLUSION: SGLT-2 inhibitors as an add-on therapy to metformin were shown to significantly improve P wave indices and atrial electromechanics in type 2 DM patients as early as the 3rd month of treatment. It was thought that this may be one of the underlying mechanisms of the decrease in the frequency of AF with the use of SGLT2 inhibitors.
Subject(s)
Atrial Fibrillation , Diabetes Mellitus, Type 2 , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Humans , Atrial Fibrillation/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Metformin/therapeutic use , Prospective Studies , Heart AtriaABSTRACT
OBJECTIVE: Contrast-induced nephropathy (CIN) is one of the well-known complications of cardiac catheterization and related with in-hospital and long-term morbidity and mortality. We aimed to evaluate if CHA2DS2-VASc score can also be used as a surrogate for CIN development and moreover the relationship between CIN development and in-hospital major adverse cardiac events (MACE) in patients presenting with STEMI and undergoing primary PCI. METHODS: All patients presented with STEMI and underwent primary PCI between 2015-2019 in our center were included retrospectively. RESULTS: A total of 572 patients were included. Age [P = 0.032, ß: 0.153, odds ratio (95% CI): 0.014-0.302], diabetes mellitus [(P = 0.023, ß: 0.134, odds ratio (95% CI): 0.017-0.217], history of stroke [P = 0.034, ß: 0.118, OR (95% CI): 0.017-0.436], volume of contrast medium [P = 0.042, ß: 0.155, OR (95% CI): 0.109-0.462], left ventricular ejection fraction [P = 0.003, ß: 0.376, OR (95% CI): 0.214-0.517], and CHA2DS2-VASc score [P = 0.001, ß: 0.115, OR (95% CI): 0.054-0.177] were detected as independent risk factors associated with contrast-induced nephropathy development. The area under the curve for CHA2DS2-VASc score was 0.809 (95% CI: 0.760-0.857). A cut-oï¬ value of 2.5 for CHA2DS2-VASc score was associated with 80.1% sensitivity and 71.4% speciï¬city in the prediction of contrast-induced nephropathy development. CONCLUSION: Our current study showed that the CHA2DS2-VASc risk score has an eï¬ective discriminating power in determining the contrast-induced nephropathy development and a score ≥2 deï¬nes the group at risk in patients presenting with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention. Moreover, contrast-induced nephropathy development is associated with longer coronary care unit stay and major adverse cardiac events (in-hospital decompensated heart failure, cardiogenic shock, cardiac arrest, and mortality).
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/surgery , Retrospective Studies , Risk Assessment , Percutaneous Coronary Intervention/adverse effects , Stroke Volume , Ventricular Function, Left , Risk FactorsABSTRACT
OBJECTIVE: Whether modiï¬ed Glasgow prognostic score predicts prognosis in patients with cardiac resynchronization therapy with deï¬brillation is unknown. Our aim was to investigate the association of modiï¬ed Glasgow prognostic score with death and hospitalization in cardiac resynchronization therapy with deï¬brillation patients. METHODS: A total of 306 heart failure with reduced ejection fraction patients who underwent cardiac resynchronization therapy with deï¬brillation implantation were categorized into 3 groups based on their modiï¬ed Glasgow prognostic score categorical levels. C-reactive protein >10 mg/L or albumin <35 g/L was assigned 1 point each and the patients were classiï¬ed into 0, 1, and 2 points, respectively. Remodeling was determined according to the clinical event and myocardial remodeling criteria. Major adverse cardiac events were deï¬ned as mortality and/or hospitalization for heart failure. RESULTS: Age, New York Heart Association functional class, modiï¬ed Glasgow prognostic score prior to cardiac resynchronization therapy with deï¬brillation, sodium levels, and left atrial diameter were higher in the major adverse cardiac events(+) group. Age, left atrial diameter, and higher modiï¬ed Glasgow prognostic score were found to be predictors of heart failure hospitalization/death in multivariable penalized Cox regression analysis. Besides, patients with lower modiï¬ed Glasgow prognostic score showed better reverse left ventricular remodeling demonstrated by increase in left ventricle ejection fraction and decline in left ventricle end systolic volume. CONCLUSION: Modiï¬ed Glasgow prognostic score prior to cardiac resynchronization therapy with deï¬brillation can be used as a predictor of long-term heart failure hospitalization and death in addition to age and left atrial diameter. These results can guide the patient selection for cardiac resynchronization therapy with deï¬brillation therapy and highlight the importance of nutritional status.
Subject(s)
Atrial Fibrillation , Cardiac Resynchronization Therapy , Heart Failure , Humans , Prognosis , Treatment Outcome , Atrial Fibrillation/therapy , Stroke Volume , Ventricular RemodelingABSTRACT
BACKGROUND The Glasgow prognostic score (GPS) consists of a combination of serum C-reactive protein and albumin levels as indicators of systematic inflammatory response and nutritional status, respectively. The present retrospective study aimed to evaluate the association between the GPS and atrial fibrillation, stroke, and mortality at 30 days and 1 year after coronary artery bypass graft (CABG) surgery. MATERIAL AND METHODS Patients with chronic coronary syndromes who underwent CABG surgery between 2012 and 2019 in a single center were included. Preoperative GPS was calculated. Then, patients were grouped according to postoperative atrial fibrillation (POAF) development. Further, groups were formed to evaluate the relationship between GPS and 30-day and 1-year cardiovascular mortality as well as stroke development. RESULTS Patients who developed POAF had higher GPS, higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score, advanced age, lower angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use, lower left ventricular ejection fraction, and were more likely to be female and to have a history of carotid artery disease (P<0.05, for all). Additionally, GPS, EuroSCORE II, advanced age, and lower left ventricular ejection fraction were detected as independent risk factors for POAF development. When adverse outcomes were assessed, cardiovascular mortality at 30 days or 1 year, and stroke development at 1 year, were more frequent in patients with POAF. Moreover, POAF development was found to be an independent risk factor for adverse outcomes. Also, GPS was established as an independent risk factor both for 30-day and 1-year cardiovascular mortality (P<0.0001 and P=0.001, respectively). CONCLUSIONS GPS is an easy-to-calculate score that has reasonable diagnostic accuracy in determining the risk of POAF and stroke as well as 30-day and 1-year cardiovascular mortality.
Subject(s)
Atrial Fibrillation , Stroke , Humans , Female , Male , Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Retrospective Studies , Prognosis , Angiotensin Receptor Antagonists , Stroke Volume , Postoperative Complications/diagnosis , Angiotensin-Converting Enzyme Inhibitors , Ventricular Function, Left , Coronary Artery Bypass/adverse effects , Risk Factors , Stroke/complicationsABSTRACT
OBJECTIVES: The main focus of this study is to evaluate the reliability and durability of saphenous vein bypass grafting from common carotid artery to internal carotid artery (CBG) asan alternative treatment of patients with carotid artery stenosis. METHODS: 459 patients with carotid artery stenosis underwent initial carotid endarterectomy (CEA) or CBG between 2009 and 2019. Propensity score matching was performed, and outcomes of two different surgical procedures were analyzed. RESULTS: Outcomes of the 142 pairs of matched patients were investigated. There were no significant differences in the preoperative characteristics of these matched groups. Overall mean time of follow-up was 91.364 ± 3.265 months. Mortality rate during the follow-up period was 18.309% (26 patients) in the CEA group, and 11.971% (17 patients) in the CBG group. Stroke was encountered in 8 patients in the CEA group (5.63%), and 3 patients in the CBG group (2.11%) during follow-up. Restenosis was detected in 11 patients in the CEA group (7.75%), and 3 patients in the CBG group (3.52%) during follow-up. There were no significant differences in the survival, stroke - free survival, and restenosis - free survival distributions of both groups. CONCLUSIONS: In carotid artery stenosis, it is reasonable to consider CBG as an alternative surgical option when adequate disease-free inflow (common carotid artery) and outflow (distal internal carotid artery) segments are present.
Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Stroke , Humans , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Propensity Score , Reproducibility of Results , Treatment Outcome , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Retrospective Studies , Risk FactorsABSTRACT
In this study, eight new compounds (7a-h) based on triazole compounds containing ester groups were synthesized with high yields. The structures of the synthesized compounds (7a-h) were elucidated by various spectroscopic methods (element analysis, FT-IR, 1H-(13C) NMR). Antioxidant, anticancer, and α-amylase enzyme inhibition activities of synthesized new triazole derivatives were carried out, and the effects of different groups on the activity were investigated. When the determined antioxidant properties of the compounds were examined, all synthesized compounds showed a moderate radical scavenging effect against radicals depending on the concentration (6.25-200 g/mL). All compounds except the three derivatives were found to have higher IC50 values than the standard drug acarbose (IC50: 891 µg/mL) according to the α-amylase enzyme inhibition results. Compound 7g (IC50: 50 g/mL) was discovered to have nearly eighteen (18) times the activity of the conventional medication acarbose (IC50: 891 µg/mL). Compounds synthesized for anticancer activity studies were screened against the Hela cell line, and the results were compared with standard cis-platinum (IC50: 16.30 µg/mL). Compound 7g (IC50: 19.78 µg/mL) was found to have almost the same activity as cis-platinum. Using Qikprop, the compounds were thoroughly tested for ADME qualities, and none violated any drug similarity standards. According to ADME data, whole physicochemical drug-likeness parameters of molecules remained within defined ranges as stipulated in the Lipinski rules (RO5) and revealed a high bioavailability profile. The molecular docking results with 2QV4 and 4GQR alpha-amylase enzymes demonstrated that all molecules have a high affinity, indicating polar and apolar interaction with critical amino acids in the α-amylase binding pocket.
Subject(s)
Acarbose , Antioxidants , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Antioxidants/pharmacology , HeLa Cells , Cisplatin , Triazoles/pharmacology , Triazoles/chemistry , Spectroscopy, Fourier Transform Infrared , alpha-Amylases/metabolism , Molecular StructureABSTRACT
Rapid and selective detection of nitroaromatic explosives is very important for public safety, life, and environmental health. Current instrumental techniques suffer from high cost and poor site used. In order to investigate fluorescence sensing of nitroaromatics, we prepare a new small fluorescence probe derived from pamoic acid. This study covers the synthesis of Pamoic acid based [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) material and characterization of its structure. The methylation of Pamoic acid ester, which we have successfully synthesized in our previous studies, was carried out in this study. Determination of the photophysical and fluorescent nitroaromatic detection properties of the compound forms the basis of the study. Structural characterization of the synthesized compound [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) was characterized using spectroscopic methods. In addition, Molecular structure of the synthesized compound was determined by single crystal X-ray diffraction studies. In the final step, compounds [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1) and [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) were tested as fluorescent probes for the detection of some nitroaromatic explosives. It is seen that Nitrobenzene provides the best quenching effect on the compound [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1) containing the -OH group, with lowest the limit of detection (LOD) value. It was observed that Picric acid provided the best quenching effect with lowest the limit of detection (LOD) value in the compound [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) obtained by methylation of the -OH group in the compound [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1).
ABSTRACT
New hybrid compounds belonging to the class of 1,4-disubstituted 1,2,3-triazoles were synthesized. The structural characterization of the synthesized compounds was performed using IR, 1H-NMR, 13C NMR and elemental analysis techniques. Diarylketones 1a and 1b were used as starting compounds for the synthesis of triazoles. The corresponding diarylmethanol derivatives (2a,b) were obtained from reduction of ketone units with NaBH4. Oxyalkynes (3a,b) were obtained by treating the hydroxyl group with NaH in anhydrous THF and then with propargylbromide. The target hybrid structures 6a-n were obtained from the metal-catalyzed "click reaction" of the arylazide and alkyne units. The newly synthesized compounds were structurally analysed using 1H-NMR, 13C-NMR, elemental analysis, LC-MS and FT-IR. The antioxidant and anticancer activities of all compounds were investigated. It has been determined that the new hybrid structures have very good antioxidant and anticancer activities according to the standards. In particular, compounds 6b, 6h, 6i and 6j (IC50: 1.87, 12.5, 7.22, 8.04 µM) showed excellent activity compared to standard 5-Fu (IC50: 40.89 µM). According to the results of molecular docking of compounds 6b and 6i with the highest cancer activity, MetAP-2 was found to have a high affinity through exposed polar and apolar contacts with fundemental residues in the binding pocket.Communicated by Ramaswamy H. Sarma.
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In this work, eight new 1,2,3-triazoles (6a-h) were synthesized from acetylenes' "click" reaction with p-substituted azide derivatives. The structures of the compounds were characterized using standard analytical and spectroscopic methods (elemental analysis, FT-IR, 1H(13C)NMR). The anticancer, antioxidant, α-amylase, ADME, molecular docking studies of synthesized triazoles were investigated. According to α -amylase enzyme inhibition results, all compounds except 6c (IC50: 2299 µg/mL) were found to have a higher IC50 value than the standard drug acarbose (IC50: 891 µg/mL). Compound 6g (IC50: 68 µg/mL) exhibited 13 times higher activity than standard acarbose. All compounds, except 6e, have been shown to have greater DPPH radical scavenging capabilities than BHT and ß-carotene standards. According to ABTS radical scavenging studies, all compounds showed higher scavenging activity than ascorbic acid and Trolox. To determine the anticancer activity of the synthesized compounds, they were screened against the Hela cell line, and the results were compared with standard cisplatin (IC50: 16.30 µg/mL). Compound 6a (IC50: 49.03 µg/mL) was determined to have moderate activity relative to cisplatin. The compounds were examined comprehensively for ADME characteristics and did not violate any drug-likeness rule. ADME data showed that all physicochemical and pharmacological parameters of the compounds remained within defined limits as specified in Lipinski's rules (RO5) and put forth a high bioavailability profile. The molecular docking findings show that all molecules have a high affinity by exhibiting polar and apolar contact with essential residues in the binding pocket of α-amylase.Communicated by Ramaswamy H. Sarma.
Subject(s)
Cisplatin , Enzyme Inhibitors , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Enzyme Inhibitors/chemistry , HeLa Cells , Acarbose , Triazoles/pharmacology , Triazoles/chemistry , Spectroscopy, Fourier Transform Infrared , alpha-Amylases , Molecular StructureABSTRACT
Introduction: Acute coronary syndromes and ischemic stroke have similar risk factors. Risk scores help to identify disease severity in both diseases. We aimed to evaluate if HEART (History, ECG, Age, Risk factors, and Troponin) score could predict re-hospitalization, recurrent cardiac/cerebrovascular events risk, and mortality within 1-year follow-up in patients presenting with acute ischemic stroke. Methods: Patients hospitalized with a diagnosis of acute ischemic stroke in our tertiary center between 2019 and 2021 were included in this retrospective study. CHA2DS2-VASc and HEART scores on admission were calculated. In-hospital, 1-month, and 1-year mortalities, as well as re-hospitalization due to recurrent ischemic (cardiac/cerebral), were defined as major adverse cardiac and cerebrovascular events (MACCE), and occurrence of MACCE was accepted as the primary endpoint of the study. Comparative statistical and regression analyses were obtained. Results: A total of 297 patients were included. The mortality rate for 30 days was 7.4% and 1 year was 20.5%. HEART and CHA2DS2-VASc scores were found independent risk factors associated with the occurrence of MACCE. Patients who experienced MACCE had higher HEART and CHA2DS2-VASc scores. Meanwhile, HEART score had better prognostic accuracy than CHA2DS2-VASc score when a cutoff value of 3.5 was set, which is associated with 84.7% sensitivity and 75.2% specificity in the prediction of MACCE. Conclusion: HEART score is effective in determining re-hospitalization and recurrent cerebral ischemic event risk as well as mortality within 30 days and 1 year in patients presenting with acute ischemic stroke. Thus, concomitant use of HEART and CHA2DS2-VASc scores may provide better characterization of worse prognosis in ischemic stroke patients with high sensitivity and specificity.