New advances in the treatments of drug-resistant tuberculosis

Mahmoud, M.; Tan, Yurong

doi:10.1080/14787210.2023.2240022

Cited by 5 publications

(3 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various types of NDDS-loaded anti-TB drugs, including nanoemulsions [ 240 ], lipid nanoparticles [ 241 ], metal-based nanoparticles [ 242 ], polymeric nanoparticles [ 240 ], and mesoporous silica nanoparticles [ 243 ]. These nanosystems have presented set of advantages and challenges towards the optimization of new approaches for TB treatment.…”

Section: Nanoscale Drug Delivery Systemsmentioning

confidence: 99%

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Carnero Canales,

Marquez Cazorla,

Marquez Cazorla

et al. 2024

Bioactive Materials

View full text Add to dashboard Cite

Section: Nanoscale Drug Delivery Systemsmentioning

confidence: 99%

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Carnero Canales,

Marquez Cazorla,

Marquez Cazorla

et al. 2024

Bioactive Materials

View full text Add to dashboard Cite

“…In particular, this approach should be considered where variations in drug response are measurable, such as, for example, drug absorption, distribution, metabolism and elimination (ADME) parameters [26][27][28][29] and also for toxicity such as drug allergy or other drug reactions or interactions [29][30][31][32][33][34]. Furthermore, the availability of alternative drugs should also be an option for patients with low response and/or toxicity to a particular leading drug for a specific disease [35][36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

Kontoghiorghes

2023

IJMS

View full text Add to dashboard Cite

The design of clinical protocols and the selection of drugs with appropriate posology are critical parameters for therapeutic outcomes. Optimal therapeutic protocols could ideally be designed in all diseases including for millions of patients affected by excess iron deposition (EID) toxicity based on personalised medicine parameters, as well as many variations and limitations. EID is an adverse prognostic factor for all diseases and especially for millions of chronically red-blood-cell-transfused patients. Differences in iron chelation therapy posology cause disappointing results in neurodegenerative diseases at low doses, but lifesaving outcomes in thalassemia major (TM) when using higher doses. In particular, the transformation of TM from a fatal to a chronic disease has been achieved using effective doses of oral deferiprone (L1), which improved compliance and cleared excess toxic iron from the heart associated with increased mortality in TM. Furthermore, effective L1 and L1/deferoxamine combination posology resulted in the complete elimination of EID and the maintenance of normal iron store levels in TM. The selection of effective chelation protocols has been monitored by MRI T2* diagnosis for EID levels in different organs. Millions of other iron-loaded patients with sickle cell anemia, myelodysplasia and haemopoietic stem cell transplantation, or non-iron-loaded categories with EID in different organs could also benefit from such chelation therapy advances. Drawbacks of chelation therapy include drug toxicity in some patients and also the wide use of suboptimal chelation protocols, resulting in ineffective therapies. Drug metabolic effects, and interactions with other metals, drugs and dietary molecules also affected iron chelation therapy. Drug selection and the identification of effective or optimal dose protocols are essential for positive therapeutic outcomes in the use of chelating drugs in TM and other iron-loaded and non-iron-loaded conditions, as well as general iron toxicity.

show abstract

“…Anti-virulence compounds represent the new frontier of antimicrobial treatment; they act on non-essential enzymes that are, however, required when the pathogen infects the host [18][19][20]. As a result, the therapeutic agent does not exert a constant, selective pressure on the microorganism, thus contributing to preventing resistance phenomena (multi-drug resistance or MDR and extensive drug resistance or XDR), a major issue for the treatment of tuberculosis [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Structural Study of a New MbtI-Inhibitor Complex: Towards an Optimized Model for Structure-Based Drug Discovery

Mori,

Villa,

Chiarelli

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

MbtI from Mycobacterium tuberculosis (Mtb) is a Mg2+-dependent salicylate synthase, belonging to the chorismate-utilizing enzyme (CUE) family. As a fundamental player in iron acquisition, MbtI promotes the survival and pathogenicity of Mtb in the infected host. Hence, it has emerged in the last decade as an innovative, potential target for the anti-virulence therapy of tuberculosis. In this context, 5-phenylfuran-2-carboxylic acids have been identified as potent MbtI inhibitors. The first co-crystal structure of MbtI in complex with a member of this class was described in 2020, showing the enzyme adopting an open configuration. Due to the high mobility of the loop adjacent to the binding pocket, large portions of the amino acid chain were not defined in the electron density map, hindering computational efforts aimed at structure-driven ligand optimization. Herein, we report a new, high-resolution co-crystal structure of MbtI with a furan-based derivative, in which the closed configuration of the enzyme allowed tracing the entirety of the active site pocket in the presence of the bound inhibitor. Moreover, we describe a new crystal structure of MbtI in open conformation and in complex with the known inhibitor methyl-AMT, suggesting that in vitro potency is not related to the observed enzyme conformation. These findings will prove fundamental to enhance the potency of this series via rational structure-based drug-design approaches.

show abstract

New advances in the treatments of drug-resistant tuberculosis

Cited by 5 publications

References 63 publications

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

Structural Study of a New MbtI-Inhibitor Complex: Towards an Optimized Model for Structure-Based Drug Discovery

Contact Info

Product

Resources

About