Rutin/Sulfobutylether-β-Cyclodextrin as a Promising Therapeutic Formulation for Ocular Infection.

Ocular pathologies present significant challenges to achieving effective therapeutic results due to various anatomical and physiological barriers. Natural products such as flavonoids, alone or in association with allopathic drugs, present many therapeutic actions including anticancer, anti-inflammatory, and antibacterial action. However, their clinical employment is challenging for scientists due to their low water solubility.

Characterization and In Vivo Antiangiogenic Activity Evaluation of Morin-Based Cyclodextrin Inclusion Complexes.

Morin (MRN) is a natural compound with antiangiogenic, antioxidant, anti-inflammatory, and anticancer activity. However, it shows a very low water solubility (28 μg/mL) that reduces its oral absorption, making bioavailability low and unpredictable. To improve MRN solubility and positively affect its biological activity, particularly its antiangiogenic activity, in this work, we prepared the inclusion complexes of MNR with sulfobutylether--cyclodextrin (SBE--CD) and hydroxypropyl--cyclodextrin (HP--CD).

1,2-Dibenzoylhydrazine as a Multi-Inhibitor Compound: A Morphological and Docking Study.

In the framework of the multitarget inhibitor study, we report an in silico analysis of 1,2-dibenzoylhydrazine (DBH) with respect to three essential receptors such as the ecdysone receptor (EcR), urease, and HIV-integrase. Starting from a crystallographic structural study of accidentally harvested crystals of this compound, we performed docking studies to evaluate the inhibitory capacity of DBH toward three selected targets. A crystal morphology prediction was then performed.

Bicalutamide Anticancer Activity Enhancement by Formulation of Soluble Inclusion Complexes with Cyclodextrins.

Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. In this work, we developed inclusion complexes of BCL with the highly soluble hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutylether-β-cyclodextrin (SBE-β-CyD) to increase the water solubility and anticancer activity of BCL.

Green Efficient One-Pot Synthesis and Separation of Nitrones in Water Assisted by a Self-Assembled Nanoreactor.

This article reports an alternative method for preparing nitrones using a tetrahedral capsule as a nanoreactor in water. Using the hydrophobic cavity of the capsule allowed us to reduce the reaction times and easily separate the nitrones from the reaction mixture, obtaining reaction yields equal or comparable to those obtained with the methods already reported. Furthermore, at the basis of this methodology, there is an eco-friendly approach carried out that can certainly be extended to other synthesis methods for the preparation of other substrates by exploiting various types of macrocyclic hosts, suitably designed and widely used in supramolecular chemistry.

Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl--Cyclodextrin Inclusion Complex †.

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl--cyclodextrin (IDE/HP--CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed.

A Pseudouridine Isoxazolidinyl Nucleoside Analogue Structural Analysis: A Morphological Approach.

An in silico study has been conducted upon (3',5')-5-[2'-benzyl-5'-hydroxymethyl-1',2'-isoxazolidin-3'-yl]uracil through a molecular dynamics/docking approach that highlights its potential inhibitory activity upon the wild-type pseudouridine 5'-monophosphate glycosidase. The crystal structure of this compound has been solved by means of X-ray single crystal diffraction and the data inferred were used to predict its crystal morphology. These data were compared with optical microscopy images and confirmed the validity of the computed models.

Gemcitabine anticancer activity enhancement by water soluble celecoxib/sulfobutyl ether-β-cyclodextrin inclusion complex.

We investigated the complexation of celecoxib (CCB) into sulfobuthyl-ether-β-cyclodextrin (SBE-β-CD) for the realization of an inhalable dry-powder formulation containing gemcitabine (GEM) for lung anticancer therapy. Complexation increased the water solubility of CCB (0.003 mg/mL and 0.

DNA intercalators based on (1,10-phenanthrolin-2-yl)isoxazolidin-5-yl core with better growth inhibition and selectivity than cisplatin upon head and neck squamous cells carcinoma.

((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2-yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar cycloaddition methodology, as DNA intercalating agents and evaluated for their anticancer activity against human cervical carcinoma HeLa and head and neck squamous cells carcinoma cell lines. The synthesized compounds exhibited good cytotoxic activity with IC better than cisplatin, used as the main and effective treatment for HNSCC, and a 24.3-72.

Novel Sigma Receptor Ligand-Nitric Oxide Photodonors: Molecular Hybrids for Double-Targeted Antiproliferative Effect.

This contribution reports the synthesis and evaluation of novel hybrid compounds that conjugate a sigma (σ) receptor pharmacophore and a nitric oxide (NO) photodonor. All compounds preserve their capability to generate NO under visible light and possess overall σ receptor nanomolar affinity, with one of them (8b) exhibiting remarkable σ receptor selectivity. Compounds 8b, 11a, and 11b were tested on tumorigenic MCF-7 and A2058 cells expressing high levels of σ and σ receptor, respectively.

Serendipitous discovery of potent human head and neck squamous cell carcinoma anti-cancer molecules: A fortunate failure of a rational molecular design.

Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity. Surprisingly, compounds 1a and 12, this last exclusively obtained in place of 1d, exhibited a very low HDAC inhibitory activity.

Molecular modeling studies of pseudouridine isoxazolidinyl nucleoside analogues as potential inhibitors of the pseudouridine 5'-monophosphate glycosidase.

In this paper, we investigated the hypothesis that pseudouridine isoxazolidinyl nucleoside analogues could act as potential inhibitors of the pseudouridine 5'-monophosphate glycosidase. This purpose was pursued using molecular modeling and in silico ADME-Tox profiling. From these studies emerged that the isoxazolidinyl derivative 1 5'-monophosphate can be effectively accommodated within the active site of the enzyme with a ligand efficiency higher than that of the natural substrate.

Hyphenated 3D-QSAR statistical model-scaffold hopping analysis for the identification of potentially potent and selective sigma-2 receptor ligands.

A 3D quantitative structure-activity relationship (3D-QSAR) model for predicting the σ receptor affinity has been constructed with the aim of providing a useful tool for the identification, design, and optimization of novel σ receptor ligands. The model has been built using a set of 500 selective σ receptor ligands recovered from the sigma-2 receptor selective ligand database (S2RSLDB) and developed with the software Forge. The present model showed high statistical quality as confirmed by its robust predictive potential and satisfactory descriptive capability.

Design, Synthesis, and Antibacterial Activity of a Multivalent Polycationic Calix[4]arene-NO Photodonor Conjugate.

The role of nitric oxide (NO) as an antimicrobial and anticancer agent continues to stimulate the search of compounds generating NO in a controlled fashion. Photochemical generators of NO are particularly appealing due to the accurate spatiotemporal control that light-triggering offers. This contribution reports a novel molecular construct in which multiple units of 3-(trifluoromethyl)-4-nitrobenzenamine NO photodonor are clustered and spatially organized by covalent linkage to a calix[4]arene scaffold bearing two quaternary ammonium groups at the lower rim.

Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review.

Small molecule inhibitors of adipocyte fatty acid binding protein 4 (FABP4) have attracted interest following the recent publications of beneficial pharmacological effects of these compounds. FABP4 is predominantly expressed in macrophages and adipose tissue where it regulates fatty acids (FAs) storage and lipolysis and is an important mediator of inflammation. In the past years, hundreds FABP4 inhibitors have been synthesized for effective atherosclerosis and diabetes treatments, including derivatives of niacin, quinoxaline, aryl-quinoline, bicyclic pyridine, urea, aromatic compounds and other novel heterocyclic compounds.

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route.

The intramolecular aldol condensation of aldohexos-5-ulose derivatives of the D- and L- stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30-38%). The results obtained, together with the previous findings for the L- and L- stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects.

5'-Spiro-cyclopropanated lactose derivatives as suitable intermediates for the chain elongation: synthesis of a new 6-deoxy-6-methyl δ-eptulose.

A δ-dicarbonyl heptose has been prepared through an electrophilic ring opening procedure of a 5'-spirocyclopropanated lactose derivative. The reported synthetic procedure outlines a new route for the transformation of this renewable disaccharide into new and interesting δ-dicarbonyl sugars, synthetic precursors of cyclitols, carba- and azasugars. The experimental results of the cyclopropanation process have been successfully rationalized by in silico studies.

Synthesis and physico-chemical characterization of a β-cyclodextrin conjugate for sustained release of Acyclovir.

We report the synthesis of an oligomeric prodrug of the antiviral agent Acyclovir (Acy) conjugated to β-cyclodextrin (β-CyD). The drug was selectively linked through a succinic spacer to one of the primary hydroxyl groups of β-CyD by ester linkage in a 1:1 molar ratio. The conjugate was purified by semipreparative reverse-phase chromatography and characterized by FAB mass spectrometry and NMR experiments.

Syntheses of isoxazoline-carbocyclic nucleosides and their antiviral evaluation: a standard protocol.

The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV.

New amphiphilic derivatives of poly(ethylene glycol) (PEG) as surface modifiers of colloidal drug carriers. III. Lipoamino acid conjugates with carboxy- and amino-PEG(5000) polymers.

Within a research directed to developing new polymeric materials, suitable for decorating the surface of colloidal drug carriers, PEG5000 polymers containing a free carboxyl or amine group at one end were conjugated to an α-lipoamino moiety (LAA). The conjugates were characterized by FT-IR, (1)H-NMR, and MALDI-TOF mass spectrometry. They showed the same profile of solubility as the parent PEGs in water and in some polar and apolar solvents of pharmaceutical use.

Recent advances in small organic molecules as DNA intercalating agents: synthesis, activity, and modeling.

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.

Prevalence of oxetanose forms in the tautomeric equilibrium of β-hydroxy-1,5-dicarbonyl monosaccharides.

The synthesis of 4-deoxy- and 4-deoxy-4-C-methylhexos-5-uloses, starting from 4-deoxyhex-4-enopyranosides, and a nuclear magnetic resonance (NMR) study of their isomeric composition are reported. The NMR spectra show that the two δ-dicarbonyl sugars exist as two anomeric α- and β-oxetanosyl forms, derived from the hemiacetalization of the C-3 hydroxyl group with the aldehydic carbon. The observed tautomeric equilibria have been rationalized with computational calculations.

Truncated phosphonated C-1'-branched N,O-nucleosides: a new class of antiviral agents.

Truncated phosphonated C-1'-branched N,O-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology, starting from N-methyl-C-(diethoxyphosphoryl)nitrone 7. Preliminary biological assays show that β-anomers are able to inhibit HIV in vitro infection at concentrations in the micromolar range. Higher SI values with respect to AZT indicated that the compounds were endowed with low cytotoxicity.

Neurotoxic properties of the anabolic androgenic steroids nandrolone and methandrostenolone in primary neuronal cultures.

Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture.