Delving into the Latest Updates on Oxiconazole Nitrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Oxiconazole Nitrate Cream, Oxiconazole nitrate (JAN/USAN)

+ [10]

Target

fungal CYP51A1

Mechanism

fungal CYP51A1 inhibitors(Fungal CYP51A1 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal Diseases

Active Indication

Mycosestinea crurisTinea Pedis+ [2]

Inactive Indication-

Originator Organization

Novartis Pharma AG

Active Organization

Hunan Zhongwei Pharmaceutical Co. Ltd.

ANI Pharmaceuticals, Inc.

Fougera Pharmaceuticals, Inc.

+ [1]

Inactive Organization

Taro Pharmaceuticals U.S.A., Inc.

Drug Highest PhaseApproved

First Approval Date

JP (01 Jan 1986),

Dermatomycoses

Regulation-

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Structure

Molecular FormulaC18H14Cl4N4O4

InChIKeyWVNOAGNOIPTWPT-NDUABGMUSA-N

CAS Registry64211-46-7

Antimicrobial resistance is a major global threat. In an attempt to discover new compounds with improved efficiency and to overcome drug resistance, a library of 3960 compounds was designed as conformationally rigid analogues of oxiconazole with 2H-chroman-4-one, azole and substituted phenyl fragments. The antifungal and antibacterial activity of the compounds was evaluated using molecular docking studies in the active site of six fungal and four bacterial proteins to establish the binding affinity of the designed ligands. In-silico ADME and Lipinski's rule were used to establish the drug-likeness properties of the compounds. This study revealed that all the designed compounds had a high binding affinity with the target proteins and formed H-bond and π-π interactions. The identified hits have been subjected to molecular dynamics simulations to study protein-ligand complex stability. This study has led to the identification of important compounds that can be developed further as therapeutic agents against pathogenic fungi and bacteria.Communicated by Ramaswamy H. Sarma.

17 Aug 2023·Microbiology spectrum

Oxiconazole Potentiates Gentamicin against Gentamicin-Resistant Staphylococcus aureus In Vitro and In Vivo.

Article

Author: Kaul, Grace ; Srinivas, Nanduri ; Ghouse, Mahammad ; Akunuri, Ravikumar ; Shukla, Manjulika ; Chopra, Sidharth ; Pawar, Gaurav ; Akhir, Abdul ; Shafi, Hasham

Amid the mounting burden of multidrug-resistant (MDR) bacterial infections on health care worldwide, drug repurposing, a time and cost-effective strategy to identify new applications for drugs approved for other indications, can effectively fill the void in the current antibiotic pipeline. In this study, we have repurposed a topical antifungal agent, oxiconazole, in combination with gentamicin against skin infections caused by multidrug-resistant Staphylococcus aureus. Oxiconazole was identified as having antibacterial activity against S. aureus via whole-cell screening assays against clinically relevant bacterial pathogens. It exhibited a potent in vitro profile, including equipotent activity against clinical drug-susceptible and -resistant S. aureus and Enterococcus spp. Checkerboard assays and time-kill kinetics studies demonstrated its concentration-dependent killing and ability to synergize with the approved antibiotics daptomycin and gentamicin against susceptible and MDR S. aureus strains. Oxiconazole also significantly eradicated preformed S. aureus biofilms in vitro. Eventually, in an assessment of its ability to generate resistant S. aureus mutants via serial passaging, oxiconazole displayed an extremely low propensity for developing stable resistance in S. aureus. Its in vivo efficacy alone and in combination with synergistic antibiotics was assessed in a murine superficial skin infection model of S. aureus, where it strongly synergized with gentamicin, exhibiting superior activity to the untreated control and drug-alone treatment groups. Thus, oxiconazole can be repurposed as an antibacterial alone and in combination with gentamicin against susceptible and gentamicin-resistant S. aureus infections. IMPORTANCE Staphylococcus aureus, which causes the majority of nosocomial and community-acquired infections globally, is a WHO high-priority pathogen for antibiotic research and development. In addition to invasive infections, it is the causative agent of moderate to severe skin infections, with an increasing prevalence of infections caused by MDR strains such as methicillin-resistant S. aureus (MRSA). Our study highlights the repurposing of oxiconazole, a topical antifungal agent, as an ideal candidate for combination therapy with gentamicin against susceptible and drug-resistant S. aureus skin infections due to its extremely low propensity for resistance generation in S. aureus, activity against MDR strains, bactericidal killing kinetics alone and in combination, broad antifungal efficacy, and excellent safety and tolerability profile.

28 Jun 2023·Molecules (Basel, Switzerland)

A Review of Biologically Active Oxime Ethers.

Review

Author: Kosmalski, Tomasz ; Kupczyk, Daria ; Studzińska, Renata ; Baumgart, Szymon ; Paprocka, Renata

Oxime ethers are a class of compounds containing the >C=N-O-R moiety. The presence of this moiety affects the biological activity of the compounds. In this review, the structures of oxime ethers with specific biological activity have been collected and presented, and bactericidal, fungicidal, antidepressant, anticancer and herbicidal activities, among others, are described. The review includes both those substances that are currently used as drugs (e.g., fluvoxamine, mayzent, ridogrel, oxiconazole), as well as non-drug structures for which various biological activity studies have been conducted. To the best of our knowledge, this is the first review of the biological activity of compounds containing such a moiety. The authors hope that this review will inspire scientists to take a greater interest in this group of compounds, as it constitutes an interesting research area.

100 Deals associated with Oxiconazole Nitrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D00885	Oxiconazole Nitrate	D01AC11 G01AF17	DB00239

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Mycoses	CN	Hunan Zhongwei Pharmaceutical Co. Ltd.	15 May 2012
tinea cruris	US	Fougera Pharmaceuticals, Inc.	30 Dec 1988
Tinea Pedis	US	Fougera Pharmaceuticals, Inc.	30 Dec 1988
Tinea Versicolor	US	Fougera Pharmaceuticals, Inc.	30 Dec 1988
Dermatomycoses	JP	Mitsubishi Tanabe Pharma Factory Ltd.	01 Jan 1986