In organic chemistry, the use of deuterium exchange as a tool to study the mechanism of chemical reaction has been well explored. Since two decades, the research focus on deuterated bioactive molecules has been gaining attention for investigating the therapeutic potential of deuterium replacement in a chemical structure. Recently, Food Drug Administration (FDA) approved the first deuterium-labeled drug "deutetrabenazine", and notified the deuterated drugs as new chemical entities (NCEs). Henceforth, the deuterium substitution driven structure activity relationship, preclinical pharmacokinetics, and toxicity studies were much initiated. Deuteration of a bioactive molecule often results in improved therapeutic efficacy due to the altered pharmacokinetic profile. This review provides a conceptual framework on the importance of deuterium atom in chemical structure of a drug, and its biological value in improved physiochemical properties, pharmacokinetics, biological target interaction, diagnosis, and toxicity. In addition, this review concisely updated the recent deuteration methods, chemical stability, challenges in drug development, deuterium-based imaging in diagnosis, and selected synthetic scheme of deuterated molecules.
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http://dx.doi.org/10.1016/j.bioorg.2023.106490 | DOI Listing |
J Neurotrauma
December 2024
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem.
View Article and Find Full Text PDFTrends Pharmacol Sci
December 2024
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:
Most solid tumors are insensitive to single-agent immunotherapy, calling for the development of combinatorial treatment regimens. Recently, Lin and collaborators developed a pharmacological platform enabling the combination of different immunotherapies into a single chemical entity. This approach may effectively circumvent obstacles associated with the simultaneous delivery of multiple immunotherapeutic agents.
View Article and Find Full Text PDFJ Colloid Interface Sci
December 2024
College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, PR China. Electronic address:
Contemporary industrial production and human activity release numerous toxins into our environment. Metal-organic frameworks (MOFs) are potential candidates for addressing these toxins due to their ultrahigh surface area, tailored pore size, and responsiveness to stimuli. With the rise of micro/nanomotor, imparting active motion to MOFs becomes crucial for efficiently performing tasks in challenging locations.
View Article and Find Full Text PDFPoult Sci
December 2024
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, PR China. Electronic address:
Toxicology
December 2024
Helmholtz Centre for Environmental Research - UFZ, Department Ecotoxicology, Leipzig, Germany; Entity of In Vitro Toxicology and Dermato-Cosmetology, Department of Pharmaceutical and Pharmacological Sciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels-Belgium.
Novel flame retardants (NFRs) have emerged as chemicals of environmental health concern due to their widespread use as an alternative to polybrominated diphenyl ethers (PBDE) in electrical and electronic devices. Humans and ecosystems are under threat because of e-waste recycling procedures that may emit NFRs and other anthropogenic chemicals into the e-waste workplace and the surrounding environment. The individual toxicity of NFRs including novel brominated flame retardants (NBFRs), their combined effects and the underlying mechanisms of toxicity have remained poorly understood.
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