Delving into the Latest Updates on Nifurtoinol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Nifurtoinol (INN), Nifuryl, Urfadyn

+ [1]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors)

Therapeutic Areas

Infectious DiseasesUrogenital Diseases

Active Indication

Urinary Tract Infections

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC9H8N4O6

InChIKeyUIDWQGRXEVDFCA-UHFFFAOYSA-N

CAS Registry1088-92-2

The progression of ovarian cancer seems to be related to HDAC1, HDAC3, and HDAC6 activity. A possible strategy for improving therapies for treating ovarian carcinoma, minimizing the preclinical screenings, is the repurposing of already approved pharmaceutical products as inhibitors of these enzymes.

Objective::

This work was aimed to implement a computational strategy for identifying new HDAC inhibitors for ovarian carcinoma treatment among approved drugs.

Method::

The CHEMBL database was used to construct training, test, and decoys sets for performing and validating HDAC1, HDAC3 and HDAC6 3D-QSAR models obtained by using the FLAP program. Docking and MD simulations were used in combination with the generated models to identify novel potential HDAC inhibitors. Cell viability assays and Western blot analyses were performed on normal and cancer cells for a direct evaluation of the anti-proliferative activity and an in vitro estimation of HDAC inhibition of the compounds selected through in silico screening.

Result::

The best quantitative prediction was obtained for the HDAC6 3D-QSAR model. The screening of approved drugs highlighted a new potential use as HDAC inhibitors for some compounds, in particular nitrofuran derivatives, usually known for their antibacterial activity and frequently used as antimicrobial adjuvant therapy in cancer treatment. Experimental evaluation of these derivatives highlighted a significant antiproliferative activity against cancer cell lines overexpressing HDAC6, and an increase in acetylated alpha-tubulin levels.

Conclusion::

Experimental results support the hypothesis of potential direct interaction of nitrofuran derivatives with HDACs. In addition to the possible repurposing of already approved drugs, this work suggests the nitro group as a new zinc-binding group, able to interact with the catalytic zinc ion of HDACs.

01 Apr 2021·Drug development researchQ3 · MEDICINE

Synthesis and in vitro antileishmanial efficacy of benzyl analogues of nifuroxazide

Q3 · MEDICINE

Article

Author: Kannigadu, Christina ; N'Da, David D. ; Aucamp, Janine

Abstract:

Leishmaniasis is a vector‐borne parasitic disease that mostly affects populations in tropical and subtropical countries. There is currently no vaccine to protect against and only a handful of drugs are available to treat this disease. Leishmaniasis is curable, but its eradication and elimination are hindered by the emergence of multidrug resistant strains of the causative pathogens, accentuating the need for new and effective antileishmanial drugs. In search for such agents, nifuroxazide, a clinical antibiotic, was evaluated through investigation of its benzyl analogues for in vitro antileishmanial efficacy against promastigotes of various Leishmania (L.) strains. The monobenzylated analogues 1 and 2 were the most potent of all, possessing nanomolar activities up to 10‐fold higher than the parent drug nifuroxazide against all three tested Leishmania strains. Both analogues stand as antipromastigote hits for further lead investigation into their potential to act as new antileishmanial agents.

01 Jul 2020·The Journal of antimicrobial chemotherapyQ2 · MEDICINE

Fluoroquinolone resistance in Escherichia coli isolates after exposure to non-fluoroquinolone antibiotics: a retrospective case–control study

Q2 · MEDICINE

Article

Author: Bruyndonckx, Robin ; Latour, Katrien ; Chaname Pinedo, Linda E ; Catry, Boudewijn ; Goossens, Herman ; Coenen, Samuel ; Abrams, Steven

Abstract:

Objectives:

To investigate whether prior exposure to non-fluoroquinolone antibiotics increases the risk of fluoroquinolone resistance in Escherichia coli.

Methods:

This was a secondary analysis of data collected retrospectively in a case–control study linking microbiological test results (isolated bacteria and their susceptibility) of urine samples routinely collected from primary, secondary and tertiary care patients in Belgium with information on prior antibiotic use at the patient level up to 1 year previously.

Results:

In urine samples from 6125 patients, 7204 E. coli isolates were retrieved [1949 fluoroquinolone-resistant isolates (cases) and 5255 fluoroquinolone-susceptible isolates (controls)]. After adjusting for potential confounders (including fluoroquinolone use) and correcting for multiple testing there were lower odds of fluoroquinolone resistance in E. coli isolates after exposure to cefazolin (OR = 0.65; 95% CI = 0.52–0.81; P = 0.00014) and higher odds after exposure to trimethoprim/sulfamethoxazole (OR = 1.56; 95% CI = 1.23–1.97; P =0.00020) or nitrofurantoin (OR = 1.50; 95% CI = 1.23–1.84; P =0.000083). A sensitivity analysis excluding samples with antibiotic use during the 6 months prior to the sampling date confirmed the higher odds of fluoroquinolone resistance after exposure to trimethoprim/sulfamethoxazole and nitrofurantoin.

Conclusions:

Assuming no residual confounding or other biases, this study suggests that exposure to non-fluoroquinolone antibiotics, i.e. trimethoprim/sulfamethoxazole and nitrofurantoin, might be causally related to fluoroquinolone resistance in E. coli isolates from urinary samples. Future prospective research is needed to confirm non-fluoroquinolone antibiotics as potential drivers of fluoroquinolone resistance.

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