Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems.

Autor: Pavlović RZ; Department of Chemistry & Biochemistry, The Ohio State University, 1100 W. 18th Avenue, Columbus, OH, 43210, USA.; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA.; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA.; Department of Materials Science and Engineering, Northwestern University, Chicago, IL, 60208, USA.; Department of Biomedical Engineering, Northwestern University, Chicago, IL, 60208, USA)., Finnegan TJ; Department of Chemistry & Biochemistry, The Ohio State University, 1100 W. 18th Avenue, Columbus, OH, 43210, USA., Metlushko A; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA.; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA.; Department of Materials Science and Engineering, Northwestern University, Chicago, IL, 60208, USA.; Department of Biomedical Engineering, Northwestern University, Chicago, IL, 60208, USA)., Hansen AL; Campus Chemical Instrument Center, The Ohio State University, Columbus, OH, 43210, USA., Waudby CA; School of Pharmacy, University College London, London, WC1N 1AX, UK., Wang X; Department of Chemistry & Biochemistry, The Ohio State University, 1100 W. 18th Avenue, Columbus, OH, 43210, USA., Hoefer N; Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43210, USA.; Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA., McComb DW; Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43210, USA.; Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA., Pavić A; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000, Belgrade, Serbia., Plackić N; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000, Belgrade, Serbia., Novaković J; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center for Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Bradić J; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center for Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Jeremić N; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center for Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Jakovljević V; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center for Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Šmit B; University of Kragujevac, Institute for Information Technologies, Department of Science, Kragujevac, Serbia)., Matić S; University of Kragujevac, Institute for Information Technologies, Department of Science, Kragujevac, Serbia)., Alvarez-Saavedra MA; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA.; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA.; Department of Materials Science and Engineering, Northwestern University, Chicago, IL, 60208, USA.; Department of Biomedical Engineering, Northwestern University, Chicago, IL, 60208, USA)., Čapo I; Department of Histology and Embryology, Medical Faculty of Novi Sad, Novi Sad, Serbia., Moore CE; Department of Chemistry & Biochemistry, The Ohio State University, 1100 W. 18th Avenue, Columbus, OH, 43210, USA., Stupp SI; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA.; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA.; Department of Materials Science and Engineering, Northwestern University, Chicago, IL, 60208, USA.; Department of Biomedical Engineering, Northwestern University, Chicago, IL, 60208, USA)., Badjić JD; Department of Chemistry & Biochemistry, The Ohio State University, 1100 W. 18th Avenue, Columbus, OH, 43210, USA.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Dec 06; Vol. 29 (68), pp. e202303374. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1002/chem.202303374
Abstrakt: We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 1 3- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [1 2 ] 6- , to be in equilibrium with monomers 1 (R) 3- (relaxed) and 1 (S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1 (R) 3- includes anticancer drug mitoxantrone (MTO 2+ ) in its pocket to give stable binary complex [MTO⊂1] - (K d =2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.
(© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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