Synthesis, biological evaluation and structure-activity relationships of 5-arylidene tetramic acids with antibacterial activity against methicillin-resistant Staphylococcus aureus.

The steady rise of the antimicrobial resistance is a major global threat to human health that requires the urgent need for novel antibiotics. In this work we report the synthesis of a small library of 3-subsituted-5-arylidene tetramic acids in order to investigate the scope of our previously established methodology via an intermediate oxazolone and their antimicrobial activity. From this series of 14 tetramic acids, 11 derivatives are novel and one of them is a Schiff base, which was structurally characterized with single-crystal X-ray analysis and NMR spectroscopy. The compounds incorporating a lipophilic acyl group at carbon-3 of the ring showed moderate to high activity with minimum inhibitory activity of 4-32 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), accompanied by no human cell toxicity and hemolytic activity within the tested concentration range. The substituent at para position of the aryl ring seemed to have no or little effect on the antimicrobial activity of these compounds.

Biomechanical properties and histological structure of sinus of Valsalva aneurysms in relation to age and region.

Information on the biomechanical properties of aortic root aneurysms that would facilitate our understanding of their rupture modes is currently unavailable. In this study, whole-thickness wall specimens from aortic root aneurysms were studied in vitro so as to compare the biomechanical properties with gross histomorphology and composition, in relation to age, region, and direction. The stress-strain relationship was determined under uniaxial loading conditions and characterized by the Fung-type material model in terms of optimized material constants; failure properties were recorded. The connective tissue contents of the basic scleroproteins were also determined through computerized histology. Aging had a deleterious influence on the tensile strength of the aneurysmal sinus tissue, causing also stiffening and reduced extensibility that was consistent with the deficient elastin and collagen contents. Direction-dependent differences were demonstrated in the noncoronary sinus, with the circumferential being stiffer and stronger than the longitudinal direction, justified by the preferred collagen reinforcement along that direction there. In the left and right coronary sinus, the material constants and failure properties were essentially the same in the two directions, justified by the arbitrary orientation of medial (collagen and elastin fibers, and cellular) components relative to the circumferential-longitudinal directions. The material characterization results afforded, and the regional and age-related differences in the strength of the sinus wall, i.e. in its capacity to withstand hemodynamic stresses, are hoped to provide novel insight into the pathophysiological mechanisms responsible for the highest incidence of ruptured aortic root aneurysms in the right coronary and noncoronary sinus.