Abstract: We report the synthesis, antioxidant and antiproliferative activity and a QSAR analysis of synthetic diphenylpropionamide derivatives. Synthesis of these compounds was achieved by direct condensation of 2,2- and 3,3-diphenylpropionic acid and appropriate amines using 1-propylphoshonic acid cyclic anhydride (PPAA) as catalyst. Compound structures were elucidated by NMR analysis and their melting points were measured. The in vitro antioxidant activity of these compounds was tested by evaluating the amount of scavenged ABTS radical and estimating ROS and NO production in LPS stimulated J774.A1 macrophages. All compounds were tested for their effect on viability of cells and results demonstrated that they are not toxic towards the cell lines used. The cytotoxic activity of all compounds was evaluated by a Brine Shrimp Test.
Abstract: Anumber of observations have lent support to a model in which thermal stress is transduced into a signal at the level of the cellular membranes. Our alternative, but not exclusive, approach is based on the concept that the initial stress-sensing events are associated with the physical state and lipid composition of cellular membranes, i.e., the subtle alteration(s) of membrane fluidity, phase state, and/or microheterogeneity may operate as a cellular thermometer. In fact, various pathological states and aging are associated with typical "membrane defects" and simultaneous dysregulation of heat shock protein synthesis. The discovery of nonproteotoxic membrane-lipid interacting compounds, capable of modulating membrane microdomains engaged in primary stress sensing may be of paramount importance for the design of new drugs with the ability to induce or attenuate the level of particular heat shock proteins.
Abstract: In the last decade or so, it has been realised that membranes do not just have a lipid-bilayer structure in which proteins are embedded or with which they associate. Structures are dynamic and contain areas of heterogeneity which are vital for their formation. In this review, we discuss some of the ways in which these dynamic and heterogeneous structures have implications during stress and in relation to certain human diseases. A particular stress is that of temperature which may instigate adaptation in poikilotherms or appropriate defensive responses during fever in mammals. Recent data emphasise the role of membranes in sensing temperature changes and in controlling a regulatory loop with chaperone proteins. This loop seems to need the existence of specific membrane microdomains and also includes association of chaperone (heat stress) proteins with the membrane. The role of microdomains is then discussed further in relation to various human pathologies such as cardiovascular disease, cancer and neurodegenerative diseases. The concept of modifying membrane lipids (lipid therapy) as a means for treating such pathologies is then introduced. Examples are given when such methods have been shown to have benefit. In order to study membrane microheterogeneity in detail and to elucidate possible molecular mechanisms that account for alteration in membrane function, new methods are needed. In the second part of the review, we discuss ultra-sensitive and ultra-resolution imaging techniques. These include atomic force microscopy, single particle tracking, single particle tracing and various modern fluorescence methods. Finally, we deal with computing simulation of membrane systems. Such methods include coarse-grain techniques and Monte Carlo which offer further advances into molecular dynamics. As computational methods advance they will have more application by revealing the very subtle interactions that take place between the lipid and protein components of membranes - and which are so essential to their function.
Abstract: Energy dispersion X-ray diffraction (EDXD) was applied to investigate the structure of partly dehydrated mixed films formed by the phospholipid dimyristoyl phosphatidylcoline (DMPC) and any of the three diastereomers of the dicationic gemini surfactant (2S,3S)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium) butane dibromide. As the surfactant to lipid molar ratio (R(S/L)) increases, the gemini monotonically solubilizes the lipid bilayer promoting the formation of a cubic phase of space group Pmn segregating from the residual lamellar phase of the lipid. Finally, at R(S/)(L) = 1, the phase transition is complete. The mixed film at the highest surfactant to lipid molar ratio (R(S/L) = 2.3) was hydrated by a vapor saturated atmosphere. At full hydration, a cubic to lamellar phase transition occurs. Coarse grain dynamic investigations, carried out as a function of both the surfactant to lipid molar ratio and the number of water molecules for amphiphile unit, allowed us to elucidate the structure of the emerging cubic phase and the hydration-induced structural pathway of the cubic to lamellar phase transition observed by EDXD.
Abstract: The appearance of compartmentalization is recognized as a key step in biogenesis. The study of the dynamical behaviour of amphiphilic close membranes at equilibrium or under some external stress (osmotic pressure or dehydration process) can be useful in order to better elucidate the role of vesicles in the origin of life and to get insight into the molecular and membrane properties that bring to a spontaneous vesicle division. A Monte Carlo approach to simulate the evolution of close membranes under an external stress will be presented. This approach is mainly based on the accepted surface energy model introduced by Helfrich (1973) and Seifert (1997a). Some preliminary results will be also illustrated and possible developments and limits of this method discussed.
Abstract: It is a long-standing and still open problem to determine the origin of biomolecular homochirality, and many scenarios have been suggested. Amphiphilic molecules are renowned for their capability to reorganize themselves in a variety of different morphologies and topologies, and for their capability to partition chemicals in well defined domains. Here a possible role for amphiphilic molecules inducing symmetry breaking is suggested in the framework of the research on origin of life.
Abstract: A selection of mono- and diacetylenic dithiafulvalenes was synthesized and employed for the construction of extended tetrathiafulvalenes (TTFs) with hexa-2,4-diyne-1,6-diylidene or deca-2,4,6,8-tetrayne-1,10-diylidene spacers between the two 1,3-dithiole rings. By stepwise acetylenic scaffolding using (E)-1,2-diethynylethene (DEE) building blocks, an extended TTF containing a total of 18 C(sp) and C(sp(2)) atoms in the spacer was prepared. The versatility of the acetylenic dithiafulvene modules was also established by the efficient synthesis of a thiophene-spaced TTF, employing a palladium-catalyzed cross-coupling reaction. The developed synthetic protocols allow functionalization of the extended TTFs in three general ways: with 1) peripheral substituents on the fulvalene cores, 2) alkynyl moieties laterally appended to the spacer, and 3) cobalt clusters involving acetylenic moieties. Strong chromophoric properties of the extended TTFs were revealed by linear and nonlinear optical spectroscopies. Extensive electrochemical studies and calculations on these compounds are also reported, as well as X-ray crystallographic analyses.
