Condensation of daunorubicin or its (13 R, S)-dihydro derivative with inosine dialdehyde in the presence of NaBH3CN yielded novel derivatives of anthracycline antibiotics with incorporated inosine residue: 3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)-hydroxymethylmorpholino-N4"]- daunorubicin and (13 R,S)-dihydro-3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)- hydroxymethylmorpholino-N4"]-daunorubicin. The compounds did not inhibit growth of Bacillus mycoides and were less cytotoxic in vitro and less toxic in vivo than the parent antibiotics.
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J Cell Mol Med
January 2025
Zhengzhou Key Laboratory of Cardiovascular Aging, Henan Province Key Laboratory for Prevention and Treatment of Coronary Heart Disease, National Health Commission key Laboratory of Cardiovascular Regenerative Medicine, Central China Fuwai Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital & Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan, China.
N6-adenosine methylation (m6A) of RNA is involved in the regulation of various diseases. However, its role in chemotherapy-related vascular endothelial injury has not yet been elucidated. We found that methyltransferase-like 3 (METTL3) expression was significantly reduced during doxorubicin (DOX)-induced apoptosis of vascular endothelial cells both in vivo and in vitro, and that silencing of METTL3 further intensified this process.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan.
The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.
View Article and Find Full Text PDFSci Rep
January 2025
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu , Tokyo, 183-8509, Japan.
Organoids are stem cell-derived three-dimensional tissue cultures composed of multiple cell types that recapitulate the morphology and functions of their in vivo counterparts. Organ-on-a-chip devices are tiny chips with interconnected wells and channels designed using a perfusion system and microfluidics to precisely mimic the in vivo physiology and mechanical forces experienced by cells in the body. These techniques have recently been used to reproduce the structure and function of organs in vitro and are expected to be promising alternatives for animal experiments in the future.
View Article and Find Full Text PDFLangmuir
January 2025
Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Shosha, Himeji, Hyogo 671-2201, Japan.
To prepare amphiphilic diblock copolymers (MP), a controlled radical polymerization approach was employed, incorporating hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) with hydrophobic poly(3-methoxypropyl acrylate) (PMPA). The synthesized diblock copolymers feature a PMPC block with a degree of polymerization (DP) of 100 and a PMPA block with DP (=) values of 171 and 552. The hydrophilic PMPC block exhibits biocompatibility, such as inhibition of platelet and protein adsorption, because of its hydrophilic pendant zwitterionic phosphorylcholine groups that have the same chemical structure as cell membrane surfaces.
View Article and Find Full Text PDFAppl Biochem Biotechnol
December 2024
Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-Daero, Deokjin-Gu Jeonju, Jeonbuk, 54896, South Korea.
This study explores the potential of vacuoles derived from Saccharomyces cerevisiae (S. cerevisiae) as a novel form of drug carrier, specifically focusing on their application in enhancing the delivery of the chemotherapeutic agent Daunorubicin (DNR). We isolated and reassembled these vacuoles, referred to as Reassembled Vacuoles (ReV), aiming to overcome the challenges of drug degradation caused by hydrolytic enzymes within traditional vacuoles.
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