Search

The interaction of small molecules with DNA plays an essential role in many biological processes. As DNA is often the target for majority of anticancer and antibiotic drugs, study about the interaction of drug and DNA has a key role in pharmacology. Moreover, understanding the interactions of small molecules with DNA is of prime significance in the rational design of more powerful and selective anticancer agents. Two of the most important and promising targets in cancer chemotherapy include DNA alkylating agents and DNA intercalators. For these last the DNA recognition is a critical step in their anti-tumor action and the intercalation is not only one kind of the interactions in DNA recognition but also a pivotal step of several clinically used anti-tumor drugs such as anthracyclines, acridines and anthraquinones. To push clinical cancer therapy, the discovery of new DNA intercalators has been considered a practical approach and a number of intercalators have been recently reported. The intercalative binding properties of such molecules can also be harnessed as diagnostic probes for DNA structure in addition to DNA-directed therapeutics. Moreover, the problem of intercalation site formation in the undistorted B-DNA of different length and sequence is matter of tremendous importance in molecular modeling studies and, nowadays, three models of DNA intercalation targets have been proposed that account for the binding features of intercalators. Finally, despite DNA being an important target for several drugs, most of the docking programs are validated only for proteins and their ligands. Therefore, a default protocol to identify DNA binding modes which uses a modified canonical DNA as receptor is needed.

The diastereoselective 1,3-dipolar cycloadditions of achiral nitrones (I) with chiral acrylamide (II) is compared with the corresponding cycloadditions of chiral nitrones (V) with methyl acrylate.

The aggregative properties of gangliosides in diluted aqueous solutions are discussed on the basis of simple and well-established thermodynamic concepts. Theoretical assumptions are compared with experimental data obtained, mainly by scattering techniques, on GM3, GM2, GM1, GD1a, GalNAc-GD1a, GD1b, GD1b lactone and GT1b gangliosides, all containing ceramide portions of similar composition, and on GM1 molecular species containing different well-defined ceramide structures. We also report on mixed aggregates with amphiphilic compounds and on the ganglioside aggregate-soluble protein interaction effects which give rise to very stable lipoproteic complexes of well-defined ganglioside-protein composition.

Homochiral functionalized pyrrolidinone and pyrrolizidinone systems have been achieved by stereoselective intramolecular oxime-olefin cycloaddition starting from homochiral amino acids, and by subsequent reduction of the obtained fused isoxazolidines.

Title 1,3-dipoles add to phenanthrene, pyrene, anthracene and perylene, but not to naphthalene and triphenylene, to give a regioisomeric monocycloadduct. Anthracene give also the two corresponding biscycloadducts. The site- and regio-selectivity of the reactions of the anthracene and pyrene is discussed in terms of FMO approximation.

Functionalized isothiazoloisoxazole-4,4-dioxide, pyrazoloisothiazole-1,1-dioxide, [1,2]thiazinoisoxazole-4,4-dioxide and benzo[1,2]thiazinoisoxazole-4,4-dioxide systems have been obtained by intramolecular 1,3-dipolar cycloaddition, starting from substituted α- and β-sulfonamides.

Mesitonitrile oxide, but not benzonitrile oxide, adds to aza-analogues of phenanthrene to give low yields of monocycloadducts. Only phenanthridine reacts with the two nitrile oxides affording phenanthridinone. 4,7-phenanthroline also gives some other minor products among which the bisadduct to a pyridine ring was isolated. The reactivity of aza-analogues under examination is discussed in terms of FMO approximation.

An efficient reaction route towards the new class of N,O-psiconucleosides has been designed, based on the 1,3-dipolar cycloaddition of C-[(tert-butyldiphenylsilyl)oxy]methyl-N-methyl nitrone with ethyl 2-acetyloxyacrylate, followed by nucleosidation. The process has been successfully applied to all pyrimidine and purine nucleobases.

A diastereo- and enantioselective synthesis of 4′-aza analogues of 2′,3′-dideoxynucleosides has been designed by the strategy of the 1,3-dipolar cycloaddition reaction of a Vasella-type nitrone. The reaction leads to (1′ R )- and (1′ S )-4′-aza analogues of 2′,3′-dideoxythimidine and fluorouridine, in enantiomerically pure forms.