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
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
116720Informations 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.