Innovative N-Acridine Thiosemicarbazones and Their Zn(II) Complexes Transmetallate with Cu(II): Redox Activity and Suppression of Detrimental Oxy-Myoglobin Oxidation

Article

作者: Azad, Mahan Gholam ; Russell, Tiffany M. ; Richardson, Vera ; Richardson, Des R. ; Kaya, Busra ; Dharmasivam, Mahendiran ; Chen, Yanbing ; Smith, Henry

The coordination chemistry and electrochemistry of novel N-acridine thiosemicarbazones (NATs) were investigated along with their redox activity, antiproliferative efficacy, transmetalation, and dissociation properties. The ability of NAT Fe(III) complexes to inhibit detrimental oxy-myoglobin (oxy-Mb) oxidation was also examined. The NATs act as tridentate ligands with a 2:1 L/Zn(II) complex crystal structure, revealing a distorted octahedral geometry, where both ligands bind Zn(II) in a meridional conformation. The NAT Fe(III) complexes exhibited fully reversible one-electron Fe^III/II couples with more positive potentials than the Fe(III) complexes of a related clinically trialed thiosemicarbazone (e.g., [Fe(DpC)₂]⁺) due to the electron-donating capacity of acridine. Surprisingly, the NAT-Zn(II) complexes showed generally greater or similar antiproliferative activity than their ligands, Cu(II), or Fe(III) complexes. This may be explained by (1) formation of a highly lipophilic Zn(II) complex that acts as a chaperone to promote cellular uptake and (2) the capacity of the Zn(II) complex to dissociate or undergo transmetalation to the redox-active Cu(II) complex. Of the NAT-Fe(III) complexes, [Fe(AOBP)₂]⁺ demonstrated a significant (p < 0.0001) improvement in preventing oxy-Mb oxidation than the Fe(III) complex of the clinically trialed thiosemicarbazone, DpC. This article advances our understanding of NAT coordination chemistry, electrochemistry, and the intriguing biological activity of their complexes.

2024-10-01·ACS Omega

Assessing the Interaction between Dodecylphosphocholine and Dodecylmaltoside Mixed Micelles as Drug Carriers with Lipid Membrane: A Coarse-Grained Molecular Dynamics Simulation

Article

作者: Gholizadeh, Atefeh ; Amjad-Iranagh, Sepideh ; Halladj, Rouein

Integrating drugs into cellular membranes efficiently is a significant challenge in drug delivery systems. This study aimed to overcome these barriers by utilizing mixed micelles to enhance drug incorporation into cell membranes. We employed coarse-grained molecular dynamics (MD) simulations to investigate the stability and efficacy of micelles composed of dodecylphosphocholine (DPC), a zwitterionic surfactant, and dodecylmaltoside (DDM), a nonionic surfactant, at various mixing ratios. Additionally, we examined the incorporation of a mutated form of Indolicidin (IND) (CP10A), an anti-HIV peptide, into these micelles. This study provides valuable insights for the development of more effective drug delivery systems by optimizing the mixing ratios of DPC and DDM. By balancing stability and penetration efficiency, these mixed micelles can improve the delivery of drugs that face challenges crossing lipid membranes. Such advancements can enhance the efficacy of treatments for various conditions, including viral infections and cancer, by ensuring that therapeutic agents reach their intended cellular targets more effectively.

2024-10-01·Journal of Atherosclerosis and Thrombosis

Stroke Research Using Administrative Claims Database in Japan: A Narrative Review

Review

作者: Imanaka, Yuichi ; Egashira, Shuhei

AIMSAlthough administrative claims databases have recently been used for clinical research in Japan, no detailed description of their utilization in stroke research is available. We reviewed stroke studies using the Diagnosis Procedure Combination (DPC), the National Database of Health Insurance Claims and Specific Health Checkups (NDB), and several commercial databases sourced from social health insurance associations, focusing on their applications and limitations.METHODSOriginal articles on stroke published by April 2024 using the DPC, NDB, and commercial databases were identified in Ovid MEDLINE. The characteristics of each database were compared in terms of comprehensiveness, traceability, baseline information, and outcome assessment in stroke research.RESULTSA total of 114 studies were included (83 for DPC, 6 for NDB, and 25 for commercial databases). The number of stroke studies using administrative databases in Japan is still approximately 10 per year, although there is a slowly increasing trend. The DPC database was utilized for short-term outcome studies because of its detailed baseline and outcome information, although the inability to track patients once they changed facilities limits their use in long-term studies. The NDB database is potentially useful for long-term studies because of its comprehensiveness and traceability, but difficulties in data access restrict its usage. The most commonly used commercial database utilizes baseline information on lifestyle and blood test data, although the lack of coverage for those over 75 years old may limit its generalizability.CONCLUSIONSAdministrative claims databases are beginning to be used in stroke research in Japan but are not yet fully utilized. Researchers need to understand their applications and limitations.

100 项与 DpC 相关的药物交易

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