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Herein, we report on the synthesis and the evaluation of preliminary antitumor properties of a small collection of platinum(II) complexes in which a cisplatin-like unit is tethered to 7- deazaadenosine through linear alkyl chains (from 1 to 6 carbon atoms) installed at the purine C6-position. The complexation is performed by exploiting the reactivity of the bidentate amino ligands (R)- and (S)-2,3-diaminopropanoic acids (DAPA) attached at the end of the alkyl chain spacer. By varying the length of the alkyl chain and the chirality of the DAPA moiety we obtained ten novel nucleoside- platinum complexes, whose anti-cancer properties have been evaluated against the A549 and Cal27 human cancer cell lines.

Herein, the synthesis of a nucleoside platinum(II) complex in which a cisplatin-like unit is joined to 7-deazaadenosine through an amino alkyl chain installed at the C6 position of purine was explored. The capability of the new complex to react with DNA purine bases was confirmed by a model reaction with deoxyguanosine monophosphate, whereas its antiproliferative activity against A549 and Cal27 human cancer cell lines was studied by sulforhodamine B assay in comparison with its unplatinated precursor and cisplatin.

This unit contains four basic protocols describing the synthesis of 5-aminoimidazole-4-carboxamide riboside (AICAR), 5-aminoimidazole-4-carboxamide riboside (ZPM), their 4-N functionalized derivatives, and two sugar-modified analogs of AICAR. The first and second basic protocols reveal the importance of solid-phase synthesis to obtain novel AICAR and ZMP imidazole-modified analogs in a short time, whereas the third and fourth basic protocols allow for the rapid preparation of 5'-F-AICAR and D-ribityl AICA.

A general synthesis of C6-pyridylpurine nucleosides is described. The reported synthetic procedure exploits the regioselective addition of pyridinyl Grignard reagents, obtained by bromine/magnesium exchange between mono- or dihalopyridines and iPrMgCl, to the C6–N1–O– moiety of nebularine N1-oxide. The regioselective transmetallation of unsymmetrical dihalopyridines with iPrMgCl allowed C6-halopyridylpurine nucleosides to be obtained through the addition of halopyridinyl Grignard reagents. The presence of a halogenated pyridine ring in these nucleosides allows for further useful synthetic transformations.

The first stage of the HIV infection requires the entry of HIV virus into host cells. This stage involves the sequential interaction of the viral envelope glycoprotein gp120 with the CD4 glycoprotein and chemokine receptors on the host cell surface. The third hyper variable region of gp120 (V3 loop) has been identified as the pivotal component of the co-receptor binding site. The V3 loop typically consists of a 35 aminoacids loop closed by two cysteines forming a disulphide bridge. As emerged from the crystal structure of gp120 complexed with the CD4 receptor and a neutralizing antibody, the V3 loop protrudes from the protein core and is involved in the binding with the co-receptor. Given the important role played by the V3 loop for HIV-1 infection and pathogenesis many efforts are being devoted to the development of drugs targeted against it. Among the most promising alternatives is the use of aptamer technology. The first anti-HIV aptamers targeted against the V3 loop appeared in the literature in 1994 when H. Hotoda (SA-1042) and J.R. Wyatt (ISIS 5320) independently showed the ability of nucleases-resistant quadruplex-forming DNA aptamers to bind the V3 loop of gp120 thus protecting CD4+ cells from HIV infection. In 2010, considering that all the gp120-binding aptamers present in the literature needed chemical modifications to improve their resistance against nucleases and to improve the kinetics of quadruplex formation, we began a study aimed at the synthesis of a series of new monomolecular analogues of SA-1042 by exploiting the Tetra-End-Linker (TEL) strategy proposed by us in 2004 [3]. In the last four years several TEL-aptamers differing for the TEL size, the polarity of the ODN strands and lipophilic ending groups or for the ODN sequence and length have been synthesized in our laboratories. The main results obtained by chemical, biophysical, biological and SAR investigation are reported in this communication. The EC50 of new TEL-aptamers is as low as 0.039 ??M.

The synthesis of 2,6-dialkyl(aryl)purine nucleosides by appli- cation of a double addition of Grignard reagents to N1-oxide purine nucleosides is described. The synthetic protocol ex- ploits the reactivity of both the C6–N1–O– and C2–N1–O– moieties of the purine base. The overall process consists of initial Grignard reagent addition to the C6 of nebularine N1-oxide followed by aromatization to give a C6-substituted nu- cleoside. Regeneration of the N1-oxide is then followed by a second Grignard addition at C2 causing the opening of the pyrimidine ring. Cyclization of the transiently opened pyrim- idine is then driven by aromatization of the system to afford the final purine system.

Tautomerism in the [1,2,4]triazolo[3,2-c][1,2,4]triazole fused aromatic system has been investigated by single-crystal X-ray analysis, UV/Vis spectroscopy and theoretical calculations on selected new heterobicycle derivatives. The reactions of 3,4-diamino-1,2,4-triazoles with acyl chlorides or acetic anhydride in pyridine at reflux led to ring closure and the fused aromatic system was obtained as the secondary amide at N2 instead of at N5 as previously reported in the literature. For the [1,2,4]triazolo[3,2-c][1,2,4]triazole system, three different tautomers can be present. Crystal structure analysis showed the presence of only one tautomer or, depending on the packing, a mixture of two; theoretical calculations supported this finding, predicting that for all the investigated compounds one tautomer is energetically disfavoured with respect to the other two. The electronic absorption spectra of some compounds show a marked solvent dependence, which has been interpreted, with the help of theoretical calculations, in terms of acid/base equilibria, which are critically dependent upon the substituents at the heterobicycle.

The X-ray crystal and molecular structure of a polyoxygenated steroid is reported.

The title compound is a polyoxygenated steroid obtained by selective chemical oxidation of 7-dehydrocholesteryl acetate. The asymmetric unit comprises three molecules of the steroid (Z' = 3) and a molecule of acetic acid which has occupancy factor 0.131 (5). The geometric parameters of the independent molecules do not reveal significant differences. In one molecule, the terminal isopropyl group is disordered over two sets of sites with occupancy ratio 0.869 (5):0.131 (5). The three molecules reveal different hydrogen-bonding patterns. Each of them is involved in an intramolecular S(6) hydrogen-bonding motif, involving hydroxy groups as donor and acceptor. In the crystal, two independent molecules form dimers through hydrogen bonding between an OH donor and an acetate carbonyl acceptor, giving rise to R2,2(16) ring patterns. A single hydrogen bond between the OH group and a ketone carbonyl group is observed between two symmetry-independent molecules.

In this work, we establish the use of surface-enhanced Raman scattering (SERS) as a label-free analytical technique for the direct detection of G-quadruplex formation. In particular, we demonstrate that SERS analysis allows the evaluation of the relative stability of G quadruplexes that differ for the number of G tetrads and investigate several structural features of quadruplexes, such as the orientation of glycosidic bonds, the identification of distortions in the sugar–phosphate backbone, and the degree of hydrogen-bond solvation. Herein, the fluctuation of the SERS spectra, due to the specific interaction of vibrational modes with the SERS-active substrate, is quantitatively analyzed before and after quadruplex formation. The results of this study suggest a perpendicular orientation of the quadruplexes (with or without the 3′-tetra end linker) with respect to the silver colloidal surface, which opens new perspectives for the use of SERS as a label-free analytical tool for the study of the binding mode between quadruplexes and their ligands.