Targeted drug delivery systems exploiting the acidic tumor microenvironment have been thriving, with responsive modifications to the active sites like hydroxyl groups enhancing stability, reducing toxicity, and boosting targeted bioavailability. Yet, the utility of hydroxyl-based acid-sensitive linkages is currently constrained by the intricacy of synthesis, questionable stability, and an inability to discern between physiological pH levels associated with health and disease. Here, we unveiled a novel hydroxyl-based acid-labile linkage, the "acetal ester bond", which not only excelled in its hypersensitive acid responsiveness, but was also facile to synthesize, with exceptionally high yields (>80 %) of final products derived from primary, linear secondary, cyclic secondary, and tertiary alcohols consistently, demonstrating its broad applicability. Further research indicated that the acetal ester bond bearing-paclitaxel conjugate (PTX-COU) with the ability to self-assembly, remained intact in simulated physiological settings, while swiftly hydrolyzed to release PTX in the acidic tumor environment within minutes, contributing to mitigated systemic toxicity and improved bioavailability. In vitro and in vivo experiments demonstrated that PTX-COU outperformed PTX in tumor growth inhibition due to drug accumulation facilitated by acid-responsive target release. This discovery offered a promising solution for pH-triggered drug release, providing new insights and methods for the development of novel targeted drug delivery systems.
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http://dx.doi.org/10.1016/j.ejmech.2024.117153 | DOI Listing |
J Org Chem
December 2024
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Gaohai Road, Guiyang 550014, P. R. China.
A copper-catalyzed regioselective annulation reaction, conducted without ligands or oxidants, has been developed for the preparation of multisubstituted furans from the readily available starting materials, β-keto esters and propargyl acetates. This process accommodates a wide range of functional groups, resulting in furan skeletons with diverse substitution patterns. The method's potential synthetic utility is highlighted by its applicability in gram-scale preparations and late-stage modifications of natural products.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6).
View Article and Find Full Text PDFRSC Adv
December 2024
Bioorganic Laboratory, Department of Chemistry, University of Delhi Delhi-110007 India
A synthesis of a small library of fluorescent 1,4-dihydropyridine nucleoside analogues has been successfully carried out under solvent-free conditions a one-pot three-component Hantzsch condensation reaction. The process involved a Ba(NO) catalyzed solvent-free reaction between 3',5'-di--acetyl-5-formyl-2'-deoxyuridine, differently substituted β-keto ester and ammonium acetate under microwave irradiation. This facile methodology yielded the desired products with very high yields (86-96%) under solvent-free reaction conditions in a short reaction time, which was followed by a simple workup.
View Article and Find Full Text PDFACS Med Chem Lett
December 2024
Usona Institute, Fitchburg, Wisconsin 53711-5300, United States.
Psychedelic compounds, particularly psilocybin and psilocin, have shown significant therapeutic potential in treating neurological and psychiatric disorders. However, their bioavailability, rapid metabolism, and stability challenges have limited their clinical use. This Patent Highlight reviews recent innovations in psychedelic drug delivery systems and the development of psilocin analogs aimed at improving their pharmacokinetic and pharmacodynamic profiles.
View Article and Find Full Text PDFChem Commun (Camb)
December 2024
EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK.
Herein, we report the first synthesis of poly(ester--vinyl acetate) epoxide/anhydride ring-opening copolymerisation and reversible addition-fragmentation chain transfer polymerisation. This was achieved using simple, robust and bifunctional alkali metal carboxylates featuring a xanthate unit.
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