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·ASAIO Journal

Does Size Matter? The Effect of Size of Distal Perfusion Catheter on Acute Limb Ischemia: A Meta-Analysis

Article

作者: Chaurasia, Sameer ; Ganapathi, Asvin M. ; Gouchoe, Doug A. ; Henn, Matthew C. ; Satyapriya, Sree ; Whitson, Bryan A. ; Mokadam, Nahush A. ; Mast, David ; Vallakati, Ajay

Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31–0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24–0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76–1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41–4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.

100 项与 DpC 相关的药物交易

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