We report the sustainable and efficient synthesis of a new type of quinoline derivatives bearing one or two SO2CF3 groups. The protocol is metal-, catalyst- and irradiation-free, involves the use of readily available and stable precursors, and avoids the formation of side products. Also, the mild conditions of the process allow the tolerance of a wide range of functional groups. © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH

Controlling chondroitin sulfates (CSs) biological functions to exploit their interesting potential biomedical applications requires a comprehensive understanding of how the specific sulfate distribution along the polysaccharide backbone can impact in their biological activities, a still challenging issue. To this aim, herein, we have applied an “holistic approach” recently developed by us to look globally how a specific sulfate distribution within CS disaccharide epitopes can direct the binding of these polysaccharides to growth factors. To do this, we have analyzed several polysaccharides of marine origin and semi-synthetic polysaccharides, the latter to isolate the structure-activity relationships of their rare, and even unnatural, sulfated disaccharide epitopes. SPR studies revealed that all the tested polysaccharides bind to FGF-2 (with exception of CS-8, CS-12 and CS- 13) according to a model in which the CSs first form a weak complex with the protein, which is followed by maturation to tight binding with kD ranging affinities from ~ 1.31 μM to 130 μM for the first step and from ~ 3.88 μM to 1.8 nM for the second one. These binding capacities are, interestingly, related with the surface charge of the 3D-structure that is modulated by the particular sulfate distribution within the disaccharide repeating-units. © 2021 by the author. Licensee MDPI, Basel, Switzerland.

The carboarylation reaction of biphenyl-alkynes was successfully triggered by electrophilic attack of 1,1-bis(triflyl)ethylene on the alkyne moiety to give polycyclic aromatic hydrocarbons (PAHs) decorated by superacidic carbon acid functionality. Neutralisation of thus obtained acids with NaHCO3 yielded the corresponding sodium salts, which showed improved solubility in both aqueous and organic solvents. © 2021 Wiley-VCH GmbH

Despite the nutritional properties of alfalfa, its production is mainly for animal feed and it is undervalued as a food source. In this study, the valorization of alfalfa as a potential source of bioactive carbohydrates [inositols, α-galactooligosaccharides (α-GOS)] is presented. A Box– Behnken experimental design was used to optimize the extraction of these carbohydrates from leaves, stems, and seeds of alfalfa by solid–liquid extraction (SLE) and microwave-assisted extraction (MAE). Optimal extraction temperatures were similar for both treatments (40◦C leaves, 80◦C seeds); however, SLE required longer times (32.5 and 60 min vs. 5 min). In general, under similar extraction conditions, MAE provided higher yields of inositols (up to twice) and α-GOS (up to 7 times); hence, MAE was selected for their extraction from 13 alfalfa samples. Pinitol was the most abundant inositol of leaves and stems (24.2–31.0 mg·g−1 and 15.5–22.5 mg·g−1, respectively) while seed extracts were rich in α-GOS, mainly in stachyose (48.8–84.7 mg·g−1). In addition, inositols and α-GOS concentrations of lyophilized MAE extracts were stable for up to 26 days at 50◦C. These findings demonstrate that alfalfa is a valuable source of bioactive carbohydrates and MAE a promising alternative technique to obtain functional extracts. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Considering the multifactorial nature of Alzheimer's disease (AD), multitarget small molecules (MTSMs) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer's disease therapy. Thus, new Pyrimidotacrines were designed and synthesized by merging pyrimidine scaffold and tacrine. Among them, 4-(4-nitrophenyl)-2-phenyl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-5-amine (4 j) was identified as less hepatotoxic than tacrine at high concentration, a submicromolar inhibitor against both acetylcholinesterase (AChE) (IC50=677±28 nM) and butyrylcholinesterase (BuChE) (IC50=756±41 nM) showing potent antioxidant properties (2.43 TE) and displaying a strong neuroprotection effect against hydrogen peroxide (H2O2) and Oligomycin Rotenone. Consequently, 4 j is a potential new hit-ligand for AD therapy for further biological exploration. © 2021 Wiley-VCH GmbH

The combination of carbohydrates with BODIPY fluorophores gives rise to a family of BODIPY-carbohydrate hybrids or glyco-BODIPYs, which mutually benefit from the encounter. Thus, from the carbohydrates standpoint, glyco-BODIPYs can be regarded as fluorescent glycoconjugate derivatives with application in imaging techniques, whereas from the fluorophore view the BODIPY-carbohydrate hybrids benefit from the biocompatibility, water-solubility, and reduced toxicity, among others, brought about by the sugar moiety. In this Account we have intended to present the collection of available methods for the synthesis of BODIPY-carbohydrate hybrids, with a focus on the chemical transformations on the BODIPY core. © 2021 The Authors. Published by The Chemical Society of Japan & Wiley-VCH GmbH

Our endeavors in the design, synthesis, and biological assessment of five-membered-ring-fused tacrines as potential therapeutic agents for Alzheimer's disease are summarized. Particularly, we have identified racemic 4-(2-methoxyphenyl)-3-methyl-2,4,6,7,8,9-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolin-5-amine, a pyranopyrazolotacrine, as having the best nontoxic profile at the highest concentrations used (300 μM); this allows cell viability, is less hepatotoxic than tacrine, and is a potent noncompetitive AChE inhibitor (IC 50 = 1.52 ± 0.49 μM). It is able to completely inhibit the Ee AChE-induced Aβ 1-40 aggregation in a statistically significant manner without affecting the Aβ 1-40 self-aggregation at 25 μM, and shows strong neuroprotective effects (EC 50 = 0.82 ± 0.17 μM). 1 Introduction 2 Furo-, Thieno-, and Pyrrolotacrines 3 Pyrazolo-, Oxazolo-, and Isoxazolotacrines 4 Indolotacrines 5 Pyrano- and Pyridopyrazolotacrines 6 Conclusions and Outlook. © 2021. Thieme. All rights reserved.

Lipopeptides are an exceptional example of amphiphilic molecules that self-assemble into functional structures with applications in the areas of nanotechnology, catalysis or medicinal chemistry. Herein, we report a library of 21 short lipopeptides, together with their supramolecular characterization and antimicrobial activity against both Gram-negative (E. coli) and Gram-positive (S. aureus) strains. This study shows that simple lipoamino acids self-assemble into micellar or vesicular structures, while incorporating dipeptides capable of stablishing hydrogen bonds results in the adoption of advanced fibrilar structures. The self-assembly effect has proven to be key to achieve antimicrobial activity. © The Royal Society of Chemistry 2021.

A synthesis of skipped 1,4-enynes through functionalization of the cyclobutene core with alkynes has been achieved, suggesting an unusual pathway of oxidative addition in tertiary iodoalkanes. This journal is © The Royal Society of Chemistry.

Cerebrovascular diseases such as ischemic stroke are known to exacerbate dementia caused by neurodegenerative pathologies such as Alzheimer’s disease (AD). Besides, the increasing number of patients surviving stroke makes it necessary to treat the co-occurrence of these two diseases with a single and combined therapy. For the development of new dual therapeutic agents, eight hybrid quinolylnitrones have been designed and synthesized by the juxtaposition of selected pharmacophores from our most advanced lead-compounds for ischemic stroke and AD treatment. Biological analyses looking for efficient neuroprotective effects in suitable phenotypic assays led us to identify MC903 as a new small quinolylnitrone for the potential dual therapy of stroke and AD, showing strong neuroprotection on (i) primary cortical neurons under oxygen–glucose deprivation/normoglycemic reoxygenation as an experimental ischemia model; (ii), neuronal line cells treated with rotenone/oligomycin A, okadaic acid or β-amyloid peptide Aβ25–35, modeling toxic insults found among the effects of AD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Hitherto unreported 2,6-dipropargyl-1,3,5,7-tetramethyl BODIPYs can be efficiently prepared by a Nicholas reaction/decomplexation protocol from 1,3,5,7-tetramethyl BODIPYs. The title compounds, which improve the BODIPY photostability by retaining their inherent photophysical and photochemical properties, can be engaged in efficient copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click-typereactions with azido derivatives to provide all-BODIPY-triads or conjugated BODIPYs. © 2021 The Authors. Published by American Chemical Society.

Multidrug resistance constitutes a serious obstacle of the treatment success of cancer by chemotherapy. Mostly it is driven by expression of ABC transport proteins that actively efflux the anticancer agents out of the cell. This work describes the design and synthesis of 12 new pyrimidopyrimidines, as well as their inhibition of ABCG2 a transporter referred also to as breast cancer resistance protein, the selectivity versus ABCB1 (P-glycoprotein/P-gp) and ABCC1 as well as the investigation of their accumulation in single cells. From these results, N-(3,5-dimethoxyphenyl)-2-methyl-7-phenyl-5-(p-tolyl)pyrimido[4,5-d]pyrimidin-4-amine 7 h was identified as promising hit that deserves further investigation showing a selective and effective inhibition of ABCG2 with IC50 equal to 0.493 µM only 2-fold less active than Ko143. © 2021 Elsevier Inc.