Cyclopentyl Methyl Ether: An Elective Ecofriendly Ethereal Solvent in Classical and Modern Organic Chemistry.

Solvents represent one of the major contributions to the environmental impact of fine-chemical synthesis. As a result, the use of environmentally friendly solvents in widely employed reactions is a challenge of vast real interest in contemporary organic chemistry. Within this Review, a great variety of examples showing how cyclopentyl methyl ether has been established as particularly useful for this purpose are reported. Indeed, its low toxicity, high boiling point, low melting point, hydrophobicity, chemical stability towards a wide range of conditions, exceptional stability towards the abstraction of hydrogen atoms, relatively low latent heat of vaporization, and the ease with which it can be recovered and recycled enable its successful employment as a solvent in a wide range of synthetic applications, including organometallic chemistry, catalysis, biphasic reactions, oxidations, and radical reactions.

Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity.

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI50 values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure features as antitubulin agents by in silico protocols.

Drugs Polypharmacology by In Silico Methods: New Opportunities in Drug Discovery.

BACKGROUND: Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug discovery industry. METHODS: Polypharmacology consists of two different approaches: the former, concerning a single drug interacting with multiple targets related to only one disease pathway; the latter, foresees a single drug's action on multiple targets involved in multiple disease pathways. Both new approaches are strictly connected to the discovery of new feasible off targets for approved drugs. RESULTS: In this review, we describe how the in silico facilities can be a crucial support in the design of polypharmacological drug. The traditional computational protocols (ligand based and structure based) can be used in the search and optimization of drugs, by using specific filters to address them against the polypharmacology (fingerprints, similarity, etc.). Moreover, we dedicated a paragraph to biological and chemical databases, due to their crucial role in polypharmacology. CONCLUSION: Multitarget activities provide the basis for drug repurposing, a slightly different issue of high interest as well, which is mostly applied on a single target involved in more than one diseases. In this contest, computational methods have raised high interest due to the reached power of hardware and software in the manipulation of data.

Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[b]thiophene derivatives.

A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed through the in silico VLAK protocol. Compounds presenting the 3,4,5-trimethoxy-benzoyl moiety were in silico classified as potential antimitotic agents or topoisomerase II inhibitors, in good agreement with the biological studies.

Does ligand symmetry play a role in the stabilization of DNA G-quadruplex host-guest complexes?

In efforts to find agents with improved biological activity against cancer cells, recent years have seen an increased interest in the study of small molecules able to bind the deoxyribonucleic acid (DNA) when it assumes secondary structures known as G-quadruplexes (G4s) preferring them over the B form. Currently, several compounds reported in literature have already shown to be good candidates as G4s DNA stabilizers. Even though some specific features for the G4s affinity are known, such as a π-delocalized system able to stack at the top/end of a G-tetrad and positively charged substituents able to interact with the grooves, it is not clear yet what kind of structural features affect more the G4 arrangement. This is mainly due to the structure heterogeneity of both the G4 stabilizer compounds and the DNA G4s isoforms. In this review, we aim to classify some known G4 binders by analyzing them from a new perspective surprisingly never approached up to date: the symmetry features. Molecular symmetry could be responsible for the specific binding mode to the G4-DNA but could also be crucial in determining different isoform affinity. We propose to classify the G4s stabilizers in five main point group symmetry classes. This classification could be useful to design new ligands able to stabilize a specific G-quadruplex isoform, in order to increase the selectivity of new potential anticancer G-quadruplex targeting drugs, a goal yet highly sought by researchers.