Delving into the Latest Updates on Eberconazole Nitrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Eberconazol, Eberconazole, WAS 2160

+ [2]

Target

fungal CYP51A1

Action

inhibitors

Mechanism

fungal CYP51A1 inhibitors(Fungal CYP51A1 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal Diseases

Active Indication

MycosesTineaTinea Pedis

Inactive Indication

Dermatophilosis

Originator Organization

Laboratorios Salvat SA

Active Organization

Laboratorios Salvat SA

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

Spain (01 Jan 2005),

MycosesTinea PedisTinea

Regulation-

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Structure/Sequence

Molecular FormulaC18H15Cl2N3O3

InChIKeyDPHMSVRBAXJSPF-UHFFFAOYSA-N

CAS Registry130104-32-4

The present study focuses on the development of a bioadhesive eutectogel (BAEgel) incorporating deep eutectic solvents (DESs) to enhance the solubility of Eberconazole (EBER), a poorly water-soluble yet highly permeable Biopharmaceutics Classification System (BCS) Class II antifungal drug. Among the various DESs evaluated, the combination of choline chloride (ChCl) and propylene glycol (PG) in a 1:2 M ratio, DES (plain) demonstrated the highest solubility for EBER, achieving 63.75 ± 3.3 mg/mL, which represents a significant enhancement. This DES-EBER system was subsequently incorporated into several BAEgel formulations prepared using various polymers such as carbopol, sodium alginate, and hydroxypropyl methylcellulose K15 (HPMC k15). Among these, the BAEgel-F5 formulation batch, comprising 2.25 % sodium alginate and 0.5 % HPMC K15, was selected based on its optimal performance. BAEgel-F5 exhibited favorable physicochemical properties, including suitable viscosity, pH, spreadability, and good drug content. In vitro drug release studies revealed a sustained release profile over 12 h, with 93.85 ± 2.81 % drug release, which was significantly higher compared to the pure drug that showed only 32.21 ± 2.46 % release. Antifungal activity studies further demonstrated that BAEgel-F5, despite containing only half the EBER concentration (0.5 %) of the marketed formulation (1 %), achieved comparable antifungal efficacy. The accelerated stability studies also revealed excellent chemical and physical stability of BAEgel-F5 formulation. Overall, this study highlights the potential of BAEgel as an effective topical delivery platform for antifungal drugs, offering improved therapeutic efficacy with lower drug concentration.

01 Aug 2024·New Microbes and New Infections

Evaluation of MMV Pandemic Response Box compounds to identify potent compounds against clinically relevant bacterial and fungal clinical isolates in vitro

Article

Author: Jeyaraj, Sankarganesh ; Sivasankar, Seshan ; Boppe, Appalaraju ; Grobusch, Martin Peter

Background:

Multidrug resistant bacterial and fungal pathogens are resistant to a number of significant front-line drugs, hence, identification of new inhibitory agents to combat them is crucial. In this study, we aim to evaluate the activity of Pandemic Box compounds from Malaria Medicines Venture (MMV) against A. baumannii and P. aeruginosa bacterial, C. auris, C. albicans and A. niger fungal clinical isolates.

Methods:

Isolates were initially screened with 201 antibacterial and 46 antifungal compounds (10 μM) using a microbroth dilution in triplicates to determine MIC. A persister assay was performed for bacterial pathogens.

Results:

Out of 201 antibacterial compounds, twenty-nine and seven compounds inhibited the growth of A. baumannii and P. aeruginosa at 10 μM, respectively. MMV1580854, MMV1579788, eravacycline and epetraborole inhibited both the bacterial test isolates. In a persister assay, MMV1634390 showed complete bactericidal effect against A. baumannii. With antifungal activity compounds, C. auris responded to15 compounds, Six compounds inhibited C. albicans and one was effective against A. niger at 10 μM. The ratio of Minimum Fungicidal Concentration (MFC): Minimum Inhibitory Concentration (MIC) of MMV1782110 was 2 against C. auris. Eberconazole, amorolfine and luliconazole are fungicidal targeting C. albicans at a MFC: MIC ratio of 2.

Conclusion:

Five compounds from MMV Pandemic Box were found to be inhibiting colistin and ceftazidime resistant A. baumannii clinical isolate, also against colistin and β-lactam resistant P. aeruginosa clinical isolate. MMV1634390 showed complete bactericidal effect against A. baumannii in a persister assay. MMV1782110, Eberconazole, amorolfine and luliconazole exhibited potent anti-fungal activity. Further investigations are warranted to identify the targets and mechanism.

01 Mar 2024·Current microbiology

Identifying Fast and Slow-Acting Antimalarial Compounds of Pandemic Response Box Against Blood-Stage Culture of Plasmodium falciparum 3D7

Article

Author: Naveen, Nimitha Cherthedath ; Rajendran, Vinoth

The evolving clinical resistance in Plasmodium falciparum and the spike in malarial cases after the COVID-19 outbreak has triggered a search for new antimalarials effective against multi-drug-resistant P. falciparum strains. In this study, we assessed the timing of action, either fast or slow-acting of 13 potent compounds of Pandemic Response Box (PRB) against blood-stage Pf3D7 strain by SYBR Green-I assay. The asynchronous culture of Pf3D7 was exposed to varying concentrations of 13 compounds, and IC₅₀ values were determined at 12, 24, 48, 72, and 96 h. We identified four fast-acting compounds (MMV000008, MMV1593541, MMV020752, MMV396785) with rapid-growth inhibitory activity having IC₅₀ values ≤ 0.3 µM at 12 and 24 h. Similarly, we determined nine slow-acting compounds (MMV159340, MMV1634492, MMV1581558, MMV689758, MMV1593540, MMV394033, MMV019724, MMV000725, MMV1557856) having IC₅₀ values ≤ 0.5 µM at 72 and 96 h. Furthermore, the stage-specific action of the two most potent fast-acting compounds (MMV1593541 and MMV020752) against rings, trophozoites, and schizonts at 48 h of exposure revealed that ring-stage parasites showed reduced IC₅₀ values compared to mature stage forms. Therefore, our study demonstrates for the first time the identification of the most potent fast and slow-acting compounds from PRB against blood-stage infection, suggesting its utility in clinics and considering it as a partner drug in combination therapies.

100 Deals associated with Eberconazole Nitrate

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