New inhibitors of homoserine dehydrogenase from Paracoccidioides brasiliensis presenting antifungal activity.
Drug discovery
Homoserine dehydrogenase
Paracoccidioides brasiliensis
Virtual screening
Journal
Journal of molecular modeling
ISSN: 0948-5023
Titre abrégé: J Mol Model
Pays: Germany
ID NLM: 9806569
Informations de publication
Date de publication:
25 Oct 2019
25 Oct 2019
Historique:
received:
08
05
2019
accepted:
30
09
2019
entrez:
27
10
2019
pubmed:
28
10
2019
medline:
4
4
2020
Statut:
epublish
Résumé
Paracoccidioidomycosis (PCM) is a systemic mycosis caused by fungi of the genus Paracoccidioides spp., which mainly affects workers in rural regions of Latin America. Although the antifungal agents currently available for the treatment of PCM are effective in controlling the disease, many months are needed for healing, making the side effects and drug interactions relevant. In addition, conventional treatments are not able to control the sequelae left by PCM, even after the cure, justifying the search for new therapeutic options against PCM. In this context, the enzyme homoserine dehydrogenase of P. brasiliensis (PbHSD) was used to screen a library of natural products from the Zinc database using three different docking programs, i.e. Autodock, Molegro, and CLC Drugdiscovery Workbench. Three molecules (Zinc codes 2123137, 15967722, and 20611644) were better ranked than the homoserine substrate (HSE) and were used for in vitro trials of the minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MCF). All three molecules presented a fungicidal profile with MICs/MCFs of 8, 32, and 128 μg mL
Identifiants
pubmed: 31654136
doi: 10.1007/s00894-019-4221-2
pii: 10.1007/s00894-019-4221-2
doi:
Substances chimiques
Antifungal Agents
0
Ligands
0
Homoserine Dehydrogenase
EC 1.1.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
325Subventions
Organisme : Fundação Araucária
ID : 147/14 and 40/16
Organisme : CAPES
ID : 001
Organisme : CNPq
ID : 305960/2015-6
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