Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents.

The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4, 8-10, 14, 17, 34, and 40 demonstrated urease inhibition in the range of IC50 = 4.4 ±â€¯0.21-115.6 ±â€¯2.13 µM, as compared to standard thiourea (IC50 = 21.3 ±â€¯1.3 µM). Especially, compound 17 (IC50 = 4.4 ±â€¯0.21 µM) was found to be five-fold more potent than the standard. Kinetic studies were also performed on compound 17 in order to identify the mechanism of inhibition. Kinetic studies revealed that compound 17 is a competitive inhibitor. Antiglycation activity was evaluated using glycation of bovine serum albumin by methylglyoxal in vitro. Compounds 2, 11-13, 16, 17, 19-22, 35, 37, and 42 showed good to moderate antiglycation activities with IC50 values of 333.63-919.72 µM, as compared to the standard rutin (IC50 = 294.46 ±â€¯1.5 µM). Results of both assays showed that the compounds with urease inhibitory activity did not show any antiglycation potential, and vice versa. Only compound 17 showed dual inhibition potential. All compounds were also evaluated for cytotoxicity. Compounds 17, 19, and 37 showed a weak toxicity towards 3 T3 mouse fibroblast cell line. All other compounds were found to be non-cytotoxic. Urease inhibition is an approach to treat infections caused by ureolytic bacteria whereas inhibition of glycation of proteins is a strategy to avoid late diabetic complications. Therefore, these compounds may serve as leads for further research.

Chiral AuI - and AuIII -Isothiourea Complexes: Synthesis, Characterization and Application.

During an investigation into the potential union of Lewis basic isothiourea organocatalysis and gold catalysis, the formation of gold-isothiourea complexes was observed. These novel gold complexes were formed in high yield and were found to be air- and moisture stable. A series of neutral and cationic chiral gold(I) and gold(III) complexes bearing enantiopure isothiourea ligands was therefore synthesized and fully characterized. The steric and electronic properties of the isothiourea ligands was assessed through calculation of their percent buried volume and the synthesis and analysis of novel iridium(I)-isothiourea carbonyl complexes. The novel gold(I)- and gold(III)-isothiourea complexes have been applied in preliminary catalytic and biological studies, and display promising preliminary levels of catalytic activity and potency towards cancerous cell lines and clinically relevant enzymes.

Frequency and predictors of non-adherence to lifestyle modifications and medications after coronary artery bypass grafting: A cross-sectional study.

BACKGROUND: Non-adherence to dietary recommendations, exercise and prescribed drug regimens, in coronary heart disease (CHD) patients following coronary artery bypass grafting (CABG), is a major health care issue worldwide. AIMS AND OBJECTIVES: The primary objective of this study was to investigate the frequency and predictors of non-adherence to lifestyle changes and medication among CHD patients after undergoing CABG surgery. METHOD: The sample of this cross sectional descriptive study was 265 patients who underwent isolated primary CABG. Participants who met the eligibility criteria were provided with a pre-coded questionnaire 4 weeks or more after surgery. Adherence was assessed on the basis of patient's self-report. Significance of results was analyzed using Chi square test. RESULTS: Roughly half of the patients were non-adherent to dietary recommendations (n=120, 45.3%) and exercise (n=109, 41.1%) while about one third (n=69, 26%) were non-adherent to prescribed medications. Unwillingness to adopt a new lifestyle and more than one social gathering per week, were found to be statistically significant predictors of non-adherence to diet (p-values<0.001). Reluctance to follow exercise regimen, busy schedule, and fear that exercise will aggravate heart issues were commonly reported as reasons for non-compliance to exercise. As for non-adherence to medication, forgetfulness, affordability of drugs and too many medications to take were important predictors. CONCLUSION: Non-adherence to lifestyle modifications and medication is an emerging problem worldwide. It is essential for medical health professionals to discuss these predictors and address them individually. Our findings highlight the need for a healthy physician and patient relationship.