Cyclodextrin-Adamantane Host–Guest Interactions on the Surface of Biocompatible Adamantyl-Modified Glycodendrimers

A series of adamantyl-modified glycodendrimers (<b>mPPI-Gx-AdaA-C</b>) was prepared in a two-step synthesis using two efficient reactions: (1) urea bond formation from amine and isocyanate and (2) reductive amination. ¹H NMR spectroscopy (host guest titration and ROESY experiments) was used to evaluate the graded effect of steric hindrance as a function of the number and type of oligosaccharide molecules and of the number of adamantyl (Ada) units on the complexation with monomeric β-cyclodextrin (β-CD). Glycosylated fourth generation PPIs showing an average substitution in adamantyl groups of 13% were found to interact with β-CD effectively, and were considered as candidates for further complexation studies with a polymeric cyclodextrin derivative (<i>poly-</i>β-CD). The host–guest interaction features of the maltosylated dense shell glycodendrimer along with the low cytotoxicity provided the rational basis for the use of these adamantyl-functionalized glycodendrimers in the design of supramolecular systems potentially useful as healthcare materials

Development of Imidazole-Reactive Molecules Leading to a New Aggregation-Induced Emission Fluorophore Based on the Cinnamic Scaffold

In order to obtain new fluorophores potentially useful in imidazole labeling and subsequent conjugation, a small series of Morita–Baylis–Hillman acetates (<b>3a–c</b>) was designed, synthesized, and reacted with imidazole. The optical properties of the corresponding imidazole derivatives <b>4a–c</b> were analyzed both in solution and in the solid state. Although the solutions display a very weak emission, the powders show a blue emission, particularly enhanced in the case of compound <b>4c</b> possessing two methoxy groups in the cinnamic scaffold. The photophysical study confirmed the hypothesis that the molecular rigidity of the solid state enhances the emission properties of these compounds by triggering the restriction of intramolecular motions, paving the way for their applications in fluorogenic labeling

Novel Dual-Acting Hybrids Targeting Type‑2 Cannabinoid Receptors and Cholinesterase Activity Show Neuroprotective Effects In Vitro and Amelioration of Cognitive Impairment In Vivo

Alzheimer’s disease (AD) is a neurodegenerative form of dementia characterized by the loss of synapses and a progressive decline in cognitive abilities. Among current treatments for AD, acetylcholinesterase (AChE) inhibitors have efficacy limited to symptom relief, with significant side effects and poor compliance. Pharmacological agents that modulate the activity of type-2 cannabinoid receptors (CB2R) of the endocannabinoid system by activating or blocking them have also been shown to be effective against neuroinflammation. Herein, we describe the design, synthesis, and pharmacological effects in vitro and in vivo of dual-acting compounds that inhibit AChE and butyrylcholinesterase (BChE) and target CB2R. Within the investigated series, compound 4g proved to be the most promising. It achieved IC50 values in the low micromolar to submicromolar range against both human cholinesterase isoforms while antagonizing CB2R with Ki of 31 nM. Interestingly, 4g showed neuroprotective effects on the SH-SY5Y cell line thanks to its ability to prevent oxidative stress-induced cell toxicity and reverse scopolamine-induced amnesia in the Y-maze forced alternation test in vivo