The present review contains a representative sampling of mechanistic studies, which have appeared in the literature in the last 5 years, on 1,3-dipolar cycloaddition reactions, using DFT ...calculations. Attention is focused on the mechanistic insights into 1,3-dipoles of propargyl/allenyl type and allyl type such as aza-ylides, nitrile oxides and azomethyne ylides and nitrones, respectively. The important role played by various metal-chiral-ligand complexes and the use of chiral eductors in promoting the site-, regio-, diastereo- and enatioselectivity of the reaction are also outlined.
Pyridine and pyrimidine derivatives have received great interest in recent pharmacological research, being effective in the treatment of various malignancies, such as myeloid leukemia, breast cancer ...and idiopathic pulmonary fibrosis. Most of the FDA approved drugs show a pyridine or pyrimidine core bearing different substituents. The aim of this review is to describe the most recent reports in this field, with reference to the newly discovered pyridineor pyrimidine-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding benzo-fused heterocyclic compounds, i.e. quinolines and quinazolines, are also reported.
Oxazole-Based Compounds As Anticancer Agents Chiacchio, Maria A; Lanza, Giuseppe; Chiacchio, Ugo ...
Current medicinal chemistry,
01/2019, Letnik:
26, Številka:
41
Journal Article
Recenzirano
Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in ...the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.
In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for ...severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNAdependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.
Boron containing compounds (BCCs) aroused increasing interest in the scientific community due to their wide application as drugs in various fields. In order to design new compounds hopefully endowed ...with pharmacological activity and also investigate their conformational behavior, the support of computational studies is crucial. Nevertheless, the suitable molecular mechanics parameterization and the force fields needed to perform these simulations are not completely available for this class of molecules. In this paper, Amber force field parameters for phenyl-, benzyl-, benzylamino-, and methylamino-boronates, a group of boron-containing compounds involved in different branches of the medicinal chemistry, were created. The robustness of the obtained data was confirmed through molecular dynamics simulations on ligand/β-lactamases covalent complexes. The ligand torsional angles, populated over the trajectory frames, were confirmed by values found in the ligand geometries, located through optimizations at the DFT/B3LYP/6-31g(d) level, using water as a solvent. In summary, this study successfully provided a library of parameters, opening the possibility to perform molecular dynamics simulations of this class of boron-containing compounds.
Schiff bases (SBs) are important ligands in coordination chemistry due to their unique structural properties. Their ability to form complexes with metal ions has been exploited for the environmental ...detection of emerging water contaminants. In this work, we evaluated the complexation ability of three newly proposed SBs,
-
, by complete conformational analysis, using a combination of Molecular Dynamics and Density Functional Theory studies, to understand their ability to coordinate toxic heavy metal (HMs) ions. From this study, it emerges that all the ligands present geometries that make them suitable to complex HMs through the
-imino moieties or, in the case of
, with the support of the oxygen atoms of the ethylene diether chain. In particular, this ligand shows the most promising coordination behavior, particularly with Pb
.
Hybrid hydrogels composed of chitosan (CS) have shown great potential in bone tissue engineering and regeneration. The introduction of polyhedral oligomeric silsesquioxanes (POSS) in the biopolymeric ...matrix has been demonstrated to improve the rheological and biological properties of the hybrid composites. In this work, we have integrated the favourable features of chitosan (CS) and POSS nanoparticles to design new nanocomposites for bone tissue regeneration, focusing our attention on the effect of POSS concentration within the CS matrix (0.5, 1, and 1.5 equivalents in weight of POSS with respect to CS) on the chemical, physical, rheological, and in vitro biological properties of the final composites. The drug release ability of the synthesized hydrogel scaffolds were also investigated using, as the model drug, ketoprofen, that was included in the scaffold during the gelling procedure, showing a more controlled release for the hybrids with respect to CS (86-91% of drug released after two weeks). The results of the in vitro biological tests performed on human fetal osteoblastic cells (hFOB 1.19) culture demonstrated the great biocompatibility of the hybrid materials. The hybrids, at the different POSS concentrations, showed values of cell mortality superimposable with control cells (11.1 vs. 9.8%), thus revealing the CS/POSS hydrogels as possible candidates for bone tissue engineering applications.
The direct oxidation reaction of isoxazolidines plays an important role in organic chemistry, leading to the synthesis of biologically active compounds. In this paper, we report a computational ...mechanistic study of RuO4-catalyzed oxidation of differently N-substituted isoxazolidines 1a–c. Attention was focused on the endo/exo oxidation selectivity. For all the investigated compounds, the exo attack is preferred to the endo one, showing exo percentages growing in parallel with the stability order of transient carbocations found along the reaction pathway. The study has been supported by experimental data that nicely confirm the modeling results.
For the first time, the tetrafluorobenzyl unit has been considered as a C-Hanion binding motif. In synergy with imidazolium groups within a bowl-shaped receptor, it has allowed for the effective ...binding of chloride in solution. Remarkable affinity was observed in organic-water mixtures.
In this paper, we report a mechanistic study of RuO4-catalyzed oxidation on the 2-methylisoxazolidine through computational methods. The investigation was performed taken into consideration that the ...oxidation could take place on different sites of the substrate. This reaction occurs in two steps, involving a double H-transfer. In particular, the rate-determining one implies a 3 + 2 one-step, but asynchronous mechanism. In the first step, when methyl propanoate is used as solvent, the formation of an ion pair, which affords to the product, is involved. Furthermore, the study highlights that all carbon atoms of the isoxazolidine system, near to the heteroatoms, can undergo the oxidation process. The detected selectivity is correlated to the stability of the corresponding carbocations, leading to the N-methylisoxazolidin-3-one as preferred product.
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