Emerging therapeutics: The imidazo[1,2-b]pyridazine scaffold as a novel drug candidate for eumycetoma, a neglected tropical disease.

Antifungal agents Drug discovery Eumycetoma Madurella mycetomatis Mycetoma Neglected tropical disease Novel therapeutics imidazo[1,2-b]pyridazine

Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
26 Jul 2024
Historique:
received: 21 06 2024
revised: 24 07 2024
accepted: 25 07 2024
medline: 15 8 2024
pubmed: 15 8 2024
entrez: 14 8 2024
Statut: aheadofprint

Résumé

Mycetoma is a neglected invasive infection endemic in tropical and subtropical regions, presenting as a chronic subcutaneous inflammatory mass that can spread to deeper structures, leading to deformities, disabilities, and potentially mortality. The current treatment of eumycetoma, the fungal form of mycetoma, involves antifungal agents, such as itraconazole, combined with surgical intervention. However, this approach has limited success, with low cure rates and a high risk of recurrence. This study addresses to the urgent need for more effective therapeutics by designing and synthesising 47 diversely pharmacomodulated imidazo [1,2-b]pyridazine derivatives using a simple synthetic pathway with good yields and purity. Of these, 17 showed promising in vitro activity against Madurella mycetomatis, the prime causative agent of eumycetoma, with IC

Identifiants

pubmed: 39142148
pii: S0223-5234(24)00601-9
doi: 10.1016/j.ejmech.2024.116720
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

116720

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Lamis Yahia Mohamed Elkheir (LYM)

The Mycetoma Research Center, University of Khartoum, Khartoum, Sudan; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Khartoum, Sudan; EA 7502 Synthèse et Isolement de Molécules Bioactives (SIMBA), University of Tours, France.

Pierre-Olivier Delaye (PO)

EA 7502 Synthèse et Isolement de Molécules Bioactives (SIMBA), University of Tours, France.

Mélanie Penichon (M)

EA 7502 Synthèse et Isolement de Molécules Bioactives (SIMBA), University of Tours, France.

Kimberly Eadie (K)

Department of Microbiology and Infectious Diseases, Erasmus Medical Center, University of Rotterdam, the Netherlands.

Magdi Awadalla Mohamed (MA)

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, KSA, Saudi Arabia.

Pierre Besson (P)

UMR INSERM U1327 ISCHEMIA "Membrane signalling and inflammation in reperfusion injuries", University of Tours, France.

Adélaïde Chesnay (A)

UMR INSERM U 1100 Centre d'Etudes des Pathologies Respiratoires, University of Tours, France.

Guillaume Desoubeaux (G)

UMR INSERM U 1100 Centre d'Etudes des Pathologies Respiratoires, University of Tours, France.

Sébastien Roger (S)

UMR INSERM U1327 ISCHEMIA "Membrane signalling and inflammation in reperfusion injuries", University of Tours, France.

Wendy Wilhelmina Johanna van de Sande (WWJ)

Department of Microbiology and Infectious Diseases, Erasmus Medical Center, University of Rotterdam, the Netherlands.

Ahmed Hassan Fahal (AH)

The Mycetoma Research Center, University of Khartoum, Khartoum, Sudan.

Cécile Enguehard-Gueiffier (C)

EA 7502 Synthèse et Isolement de Molécules Bioactives (SIMBA), University of Tours, France. Electronic address: cecile.gueiffier@univ-tours.fr.

Classifications MeSH