Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines.

We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism.

Two-dimensional supramolecular assemblies involving neoglycoplipids: Self-organization and insertion properties into Langmuir monolayers.

In nature, interfacial molecular recognition and chirality are of fundamental significance for the construction of biological assemblies. Lipid monolayers at liquid interface can be used as biomimetic models for studying molecular interactions in such assemblies. In this article, we will focus on the use of Langmuir monolayers for studying self-organization and insertion properties of several neoglycolipids. Two types of glycolipids have been considered, one in the context of the analysis of glycoconjugates of biological relevance, and one dealing with the ability of some glycoprobes to insert into a monolayer in relation with their efficiency for serving as membrane imaging systems.

Neutral push-pull chromophores for nonlinear optical imaging of cell membranes.

A new class of push-pull molecules was recently identified, based on pyridine dicarboxamide as an electron acceptor group and bearing a fluorenethynyl pi-conjugated bridge. The molecules present good second and third order nonlinear properties, with a static quadratic hyperpolarisability mubeta (at 1.907 microm) of 320 x 10(-48) esu (mubeta(0) = 249 x 10(-48) esu) and a maximum two-photon absorption cross-section of 1146 GM. Starting from this generic structure, we designed a series of eight amphiphilic nonlinear probes, varying the length of the lipophilic tail and the nature of the polar head, and tested their cell membrane affinity by nonlinear optical imaging. A good membrane affinity was observed with probes bearing short alkyl chains and carbohydrate moieties as the polar head, emphasizing the importance of the lipophilic-hydrophilic balance, as well as the role of the polar head. This original approach based on carbohydrate head groups is an important advancement in the design of membrane probes, since these highly versatile functional groups confer adequate hydrophilicity and yet conserve overall molecular neutrality.

Recent progress in the synthesis of carbohydrate-based amphiphilic materials: the examples of sucrose and isomaltulose.

In the context of the use of carbohydrates obtained from agricultural crops, the search for amphiphilic derivatives is one of the most developed aspects. Indeed, due to the high polarity and the functional richness of sugars, many different structures can be targeted, with a wide range of physicochemical properties, either for large scale products of industrial interest, or for fine applications at the chemistry-biology interface. Among carbohydrates arising from agricultural resources, sucrose is especially interesting because of its very large production scale in the world (ca. 160Mt/year, ca. 20Mt/year of which in the European Community). Here, we describe the research accomplished in our group dealing with the synthesis and the study of the properties of amphiphilic derivatives prepared from sucrose as well as from another very available disaccharide, isomaltulose.