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In this report, we discuss the synthesis of a compound obtained from the derivatization of the natural compound celastrol. This derivative is connected to PEG azide moiety through an amide linkage. The linkage was achieved through the activation of the carboxylic acid using HOBt/EDC. The compound was fully characterized by proton (1H), carbon-13 (13C), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), and distortionless enhancement by polarization transfer (DEPT) NMR. Ultraviolet (UV), Fourier-transform infrared (FTIR), and high-resolution mass spectrometry (HRMS) were also adopted. Computational investigations were conducted to forecast the binding mode between the synthesized compound and sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a known target for the development of novel therapeutics for rheumatoid arthritis. Additionally, the drug-likeness of the synthesized compound was assessed by predicting its pharmacokinetic properties. [ABSTRACT FROM AUTHOR]

We herein report the synthesis of a derivative of the natural compound celastrol linked to the antimalarial drug primaquine through an amide obtained by the activation of the carboxylic acid with HOBt/EDC. The chemical structure of the new molecule was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), distortionless enhancement by polarization transfer (DEPT), mass spectrometry, Fourier-transform infrared (FTIR), and ultraviolet (UV) spectroscopies. Computational studies were enrolled to predict the interaction of the synthesized compound with sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a target of relevance for developing new therapeutics against arthritis. The drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties. [ABSTRACT FROM AUTHOR]

We herein report on the synthesis of a pentacyclic triterpene functionalized through derivation of betulinic acid with hydroxybenzotriazole. The compound was fully characterized by proton (1H-NMR), carbon-13 (13C-NMR), heteronuclear single quantum coherence (HSQC) and distortionless enhancement by polarization transfer (DEPT-135 and DEPT-90) nuclear magnetic resonance. Ultraviolet (UV), and Fourier-transform infrared (FTIR) spectroscopies as well as and high-resolution mass spectrometry (HRMS) were also adopted. Computational studies were conducted to foresee the interactions between compound 3 and phosphodiesterase 9, a relevant target in the field of neurodegenerative diseases. Additionally, preliminary calculation of physico-chemical descriptors was performed to evaluate the drug-likeness of compound 3. [ABSTRACT FROM AUTHOR]

The 1,2,3-triazole ring system can be easily obtained by widely used copper-catalyzed click reaction of azides with alkynes. 1,2,3-triazole exhibits myriad of biological activities, including antibacterial antimalarial, and antiviral activities. We herein reported the synthesis of quinoline-based [1,2,3]-triazole hybrid derivative via Cu(I)-catalyzed click reaction of 4-azido-7-chloroquinoline with alkyne derivative of hydroxybenzotriazole (HOBt). The compound was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), correlated spectroscopy (1H-1H-COSY), heteronuclear single quantum coherence (HSQC) and distortionless enhancement by polarization transfer (DEPT-135 and DEPT-90) NMR, ultraviolet (UV) and Fourier-transform infrared (FTIR) spectroscopies, and high-resolution mass spectrometry (HRMS). Computational studies were enrolled to predict the interaction of the synthesized compound with acetylcholinesterase, a target of primary relevance for developing new therapeutic options to counteract neurodegeneration. Moreover, the drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties. [ABSTRACT FROM AUTHOR]

In drug discovery, ligand-mediated stabilization of G-quadruplexes is pursued for regulating gene expression and key cellular processes. Electrospray ionization mass spectrometry (ESI-MS) has been optimized for screening putative DNA-binding small molecules of natural and synthetic origin. Several flavonoids were reported to interact with G-quadruplex, and quercetin is among them. In this contribution, the interaction with G-quadruplex DNA of rutin, a glycoside of quercetin extracted from flower buds of Styphnolobium japonicum (L.) Schott, was investigated by means of ESI-MS and molecular docking. While rutin and quercetin showed similar G-quadruplex binding affinity values, rutin was characterized by enhanced selectivity for G-quadruplex over double stranded DNA. Moreover, collision-induced dissociation (CID) assays demonstrated that rutin stabilizes the G-quadruplex arrangement more efficiently, and molecular docking predicted stacking as the preferential interaction pattern. [ABSTRACT FROM AUTHOR]

Natural and synthetic small molecules targeting G-quadruplex are currently being studied. These peculiar DNA arrangements arise in guanine-rich sequences located in telomeres, oncogene promoters and in several viruses. Two semi-synthetic derivatives of osajin, a natural isoflavone from Maclura pomifera, were prepared and screened for their binding affinity towards G-quadruplex and double stranded DNA (dsDNA) using electrospray mass spectrometry (ESI-MS). Although an overall decrease in affinity for DNA was observed, one of the derivatives showed improved selectivity for G-quadruplex over dsDNA, retaining structure stabilization properties. Binding motif was studied by collision-induced dissociation (CID) assays and molecular docking, that suggested stacking as the preferential interaction pattern. Moreover, the compound selectively induced DNA damage on the G-quadruplex sequence upon UV irradiation, due to the presence of the photoreactive aryl tosylate group. [ABSTRACT FROM AUTHOR]

G-quadruplex DNA stabilization mediated by small molecules is an attractive approach to modulate the transcription of guanine-rich sequences and contrast unregulated cell proliferation. Natural alkaloids have been reported to target this macromolecular arrangement, and such mechanism may be among these underlying the antiproliferative effect of some flavonoids. The binding affinity for G-quadruplex and double stranded DNA of 4 isoflavones from Maclura pomifera, namely osajin, pomiferin, scandenone and auriculasin, was evaluated using electrospray mass spectrometry (ESI-MS). The experiments pointed out that osajin and scandenone preferentially bind G-quadruplex. Moreover, since G-quadruplex stabilization is a crucial aim for triggering biological effects such as gene expression, collision-induced dissociation (CID) assays were performed to study the relative gas-phase kinetic stability of the DNA/ligand complexes. Osajin was identified as the best G-quadruplex stabilizer of the set, and in silico docking studies indicate that stacking is the preferred interaction motif of this natural compound. [ABSTRACT FROM AUTHOR]

A series of new anthracene‐propargylamine derivatives were obtained through an efficient synthesis based on the A3 coupling reaction. This set of planar molecules were designed to bind double stranded and G‐quadruplex DNA arrangements. Their interaction pattern of the small molecules with DNA was predicted by molecular docking and their theoretical pharmacokinetic properties were calculated, giving encouraging results in terms of drug‐likeness. The general preference for double stranded DNA suggested by docking experiments was supported by a set of electrospray ionization mass spectrometry (ESI‐MS) experiments. [ABSTRACT FROM AUTHOR]

We discuss a novel selenium-based reaction mechanism consisting in a selenoxide elimination-triggered enamine hydrolysis. This one-pot model reaction was studied for a set of substrates. Under oxidative conditions, we observed and characterized the formation of primary and secondary amines as elimination products of such compounds, paving the way for a novel strategy to selectively release bioactive molecules. The underlying mechanism was investigated using NMR, mass spectrometry and density functional theory (DFT). [ABSTRACT FROM AUTHOR]

On the basis of the knowledge from traditional herbal and folk medicine, flavonoids are among the most studied chemical classes of natural compounds for their potential activity as phosphodiesterase 5 (PDE5) inhibitors. We here describe the preparation of a semi-synthetic hydrazone derivative of quercetin, 2-(3,4-dihydroxyphenyl)-4-(2-(4-nitrophenyl)hydrazono)-4H-chromene-3,5,7-triol, that was obtained via a single-step modification of the natural compound. The product was characterized by NMR, mass spectrometry and HPLC. Preliminary molecular modeling studies suggest that this compound could efficiently interact with PDE5. [ABSTRACT FROM AUTHOR]

G-quadruplex DNA is the target of several natural and synthetic small molecules with antiproliferative and antiviral activity. We here report the synthesis through Sonogashira reaction and A3 coupling of a disubstituted anthracene derivative, 9,10-bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene. The binding of this compound to G-quadruplex and double stranded DNA sequences was evaluated using electrospray ionization mass spectrometry (ESI-MS), demonstrating selectivity for the first structure. The interaction pattern of the ligand with G-quadruplex was investigated by molecular docking and stacking was found to be the preferred binding mode. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article XRF mapping and TEM analysis of coated and uncoated silica nanoparticles in A549 cells and human monocytes, by Iria M. Rio‐Echevarria et al., https://doi.org/10.1002/xrs.2999. Acknowledgments: Dr. George Kourousias (Elettra Sincrotrone Trieste). [ABSTRACT FROM AUTHOR]