L-Proline-catalysed synthesis of chromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione and an anti-proliferative study.

The reactivity of 4-hydroxy-2H-chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3-b]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.

Sporadic Multicentric Right Atrial and Right Ventricular Myxoma Presenting as Acute Pulmonary Thromboembolism.

Multicentric cardiac myxoma is a rare syndrome; usually it is familial. We report a rare case of sporadic right atrium (RA) and right ventricle (RV) myxoma in a 26-year-old female presenting to our hospital for the evaluation of sudden onset of dyspnea and left precordial pain attributed to the embolization of degenerating tumor fragments to the pulmonary artery (PA). The exact incidence of sporadic multicentric RA and RV myxoma presenting as acute pulmonary embolism is unknown as multicentric RA and RV myxoma are very rare. Myxomas presenting as pulmonary embolism is <10%. Majority of cardiac myxomas present as exertional dyspnea, chest pain, positional syncope, fever, weight loss and other constitutional symptoms. Any young patient presenting with acute onset dyspnea with multiple cardiac masses may have tumor embolization to the PA diagnosis with transthoracic echocardiography and high-resolution computed tomography of thorax, fast-tracks patient transfer for urgent cardiac surgery to prevent further embolization.

Differential release kinetics of cardiac biomarkers in off-pump coronary bypass.

BACKGROUND: Differential release kinetics of the cardiac biomarkers (B-type natriuretic peptide, troponin I, and creatine kinase-MB) following off-pump coronary artery bypass are not well characterized. METHODS: Biomarker levels were assessed at 6, 24, 48 h, and 1 month preoperatively, in 80 patients who underwent off-pump coronary artery bypass. RESULTS: All biomarkers increased within 6 h of surgery. Peak B-type natriuretic peptide levels occurred at 24-48 h in 96% of patients, but only two-thirds had peak troponin I and creatine kinase-MB levels at this time, reflecting different release patterns. Levels of all biomarkers declined within 48 h, but 42% of patients still had B-type natriuretic peptide >100 pg·mL(-1) at 1 month. Those with baseline B-type natriuretic peptide > 100 pg·mL(-1) had a lower left ventricular ejection fraction (43.6% vs. 55.6%, p < 0.01) and longer inotropic (43.8 vs. 31.4 h, p = 0.03) and ventilator support (34 vs. 25.5 h, p = 0.04) than those with lower levels. B-type natriuretic peptide levels correlated positively with angiographic Syntax score (p = 0.02) and negatively with left ventricular ejection fraction (p < 0.001). Only baseline B-type natriuretic peptide predicted the durations of inotropic support (p = 0.01) and ventilation (p = 0.02). Postoperative B-type natriuretic peptide at 6, 24, and 48 h and delta B-type natriuretic peptide were significant predictors of mean ventilation time. CONCLUSION: Even in patients undergoing off-pump surgery, there is significant natriuretic peptide and myocardial enzyme release. Only B-type natriuretic peptide levels had an association with postoperative variables.

Differential Release Kinetics of Cardiac Biomarkers in Patients Undergoing Valve Replacement Surgery.

BACKGROUND: Differential release kinetics of cardiac biomarkers including brain natriuretic peptide (BNP), Troponin-I, and CK-MB following valve replacement (VR) are not well characterized. METHODS AND RESULTS: We serially measured these biomarkers 24 hours prior, six hours, 24 hours, 48 hours, and one month following mitral/aortic VR in 100 patients. Baseline BNP, Tn-I, and CK-MB levels were 304.01 pg/mL, 0.03 ng/mL, and 0.99 ng/mL, respectively. While BNP levels decreased at six hours, and then peaked at 24 hours, Tn-I and CK-MB levels increased within six hours and then showed declining trends by 24 hours. While Tn-I and CK-MB levels normalized at one month, 33% patients still had BNP >200 pg/mL. Those with baseline BNP >200 pg/mL more commonly had AF, higher RV systolic pressure, longer inotrope and ventilator duration, and longer mean ICU/hospital stay as compared to those with lower BNP, although echocardiographic left ventricular ejection fraction and Tn-I/CK-MB levels were similar. Inotrope duration >42 hours, ventilation time >29 hours, and ICU stay >4 days was seen in 42% versus 19%, 30% versus 9%, and 33% versus 14%, respectively, in those with BNP >/<200 pg/mL. Baseline BNP had a significant positive correlation with mean inotrope duration, ICU, and hospital stay. Baseline BNP was also a significant predictor of inotrope duration (odds ratio [OR]=5.9, 95% confidence interval [CI]=1.20-29.68, p=0.01) and ventilation time (OR=4.7, 95% CI=1.76-17.21, p=0.02). CONCLUSION: Release kinetics of cardiac biomarkers is significantly different following VR; BNP levels increase following an initial transient decline. Only BNP was a predictor of postoperative variables.

Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents.

6-Chloro-2-pyrrolidino-/morpholino-/piperidino-/N-methylpiperazino-3-formyl-chromones (13-16) and 6-fluoro-2,7-di-morpholino-/piperidino-/N-methylpiperazino-3-formylchromones (17-19) have been synthesized as potential topoisomerase inhibitor anticancer agents, and evaluated, in vitro, against Ehrlich ascites carcinoma (EAC) cells, and also in vivo on EAC bearing mice. The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design.