The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria.

The bengamides comprise an interesting family of natural products isolated from sponges belonging to the prolific Jaspidae family. Their outstanding antitumor properties, coupled with their unique mechanism of action and unprecedented molecular structures, have prompted an intense research activity directed towards their total syntheses, analogue design, and biological evaluations for their development as new anticancer agents. Together with these biological studies in cancer research, in recent years, the bengamides have been identified as potential antibiotics by their impressive biological activities against various drug-resistant bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus. This review reports on the new advances in the chemistry and biology of the bengamides during the last years, paying special attention to their development as promising new antibiotics. Thus, the evolution of the bengamides from their initial exploration as antitumor agents up to their current status as antibiotics is described in detail, highlighting the manifold value of these marine natural products as valid hits in medicinal chemistry.

Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line.

Nanoparticle-based nanocarriers represent a viable alternative to conventional direct administration in cancer cells. This advanced approach employs the use of nanotechnology to transport therapeutic agents directly to cancer cells, thereby reducing the risk of damage to healthy cells and enhancing the efficacy of treatment. By approving nanoparticle-based nanocarriers, the potential for targeted, effective treatment is greatly increased. The so-called carbon-based nanoparticles, or carbon dots, have been hydrothermally prepared and initiated by a polymerization process. We synthesized and characterized nanoparticles of 2-acrylamido-2-methylpropanesulfonic acid, which showed biocompatibility with glioblastoma cells, and further, we tested them as a carrier for the drug riluzole. The obtained nanoparticles have been extensively characterized by techniques to obtain the exact composition of their surface by using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR) spectroscopy, as well as cryo-transmission electron microscopy. We found that the surface of the synthesized nanoparticles (NPs) is covered mainly by sulfonated, carboxylic, and substituted amide groups. These functional groups make them suitable as carriers for drug delivery in cancer cells. Specifically, we have successfully utilized the NPs as a delivery system for the drug riluzole, which has shown efficacy in treating glioblastoma cancer cells. The effect of nanoparticles as carriers for the riluzole system on glioblastoma cells was studied using live-cell synchrotron-based FTIR microspectroscopy to monitor in situ biochemical changes. After applying nanoparticles as nanocarriers, we have observed changes in all biomacromolecules, including the nucleic acids and protein conformation. These findings provide a strong foundation for further exploration into the development of targeted treatments for glioblastoma.

7-Azido-N,N-diethyl-4,5-O-isopropyl-idene-4-C-methyl-3,6-anhydro-7-de-oxy-d-glycero-d-manno-heptonamide.

The reaction of 5-azido-5-de-oxy-2,3-O-isopropyl-idene-2-C-methyl-d-ribose with N,N-diethyl-2-(dimethyl-sulfuranyl-idene)acetamide gave the title compound, C(15)H(26)N(4)O(5), as the major product arising from initial formation of an epoxide which was subsequently opened by intra-molecular attack of the free 4-hydroxyl group. X-ray crystallography confirmed the relative stereochemistry of the title compound and the absolute configuration was determined by the use of d-ribose as the starting material. The crystal structure contains chains of mol-ecules running parallel to the a axis, being linked by weak bifurcated O-H⋯(N,N) hydrogen bonds.

Rationalizing the catalytic activity of copper in the cycloaddition of azide and alkynes (CuAAC) with the topology of ∇(2)ρ(r) and ∇∇(2)ρ(r).

The distinct role of the Cu(I) in the Huisgen dipolar cycloaddition of azides to alkynes (denoted as CuAAC) is disclosed by following the evolution of the topology of the Laplacian of the electronic charge density, ∇(2)ρ(r), and its gradient vector field, ∇∇(2)ρ(r), along the reaction coordinate with several density functionals (wB97XD, LCwPBE, M06-2X, M06-L, B3LYP) and the 6-311++G(d,p) basis set. Remarkably, in view of the topology of ∇(2)ρ(r) and ∇∇(2)ρ(r), the mechanism appears to be diverse (asynchronous concerted or stepwise) depending on the reaction conditions. Overall, the catalyst orchestrates first the formation of the external N-C and subsequently the internal one by following alternatively a pericyclic-like or a pseudopericyclic-like mechanism. The role of the catalyst is envisaged as transforming the type of the mechanism from pericyclic to pseudopericyclic, and thence eventually facilitating the process. The mononuclear process (CuAAC) is concerted (with L = CH3CN) with all the functionals tested (i.e., wB97XD, LCwPBE, M06-2X, M06-L), except for the B3LYP who rendered a stepwise mechanism. Nevertheless, with L = H2O and CH3OH attached to the copper, the process becomes asynchronous concerted. Interestingly, upon introduction of the second Cu (Cu2AAC) at our best theory level (i.e., LCwPBE/6-311++G(d,p)), all the processes considered turned out to be concerted except for the 1,4-Cu2AAC which is predicted to be stepwise, with an extremely low enthalpy for the ring-contraction process (0.18 kcal/mol). This fact is explicated by the stability of the intermediate, which is in turn rationalized by the hole within the valence shell of the carbon attached to the Cu and the position of the (3, -3)LP, of the internal N, toward it. Furthermore, due to the tiny energy difference between the stepwise dinuclear and concerted mononuclear mechanisms (0.39 kcal/mol), we argue that the concurrence of both processes (CuAAC and Cu2AAC) is feasible.