Identification of a new antifungal compound against isocitrate lyase of Paracoccidioides brasiliensis.
Future Microbiol
; 14: 1589-1606, 2019 12.
Article
in En
| MEDLINE
| ID: mdl-31990208
ABSTRACT
Aim:
To perform virtual screening of compounds based on natural products targeting isocitrate lyase of Paracoccidioides brasiliensis. Materials &methods:
Homology modeling and molecular dynamics simulations were applied in order to obtain conformational models for virtual screening. The selected hits were tested in vitro against enzymatic activity of ICL of the dimorphic fungus P. brasiliensis and growth of the Paracoccidioides spp. The cytotoxicity and selectivity index of the compounds were defined. Results &conclusion:
Carboxamide, lactone and ß-carboline moieties were identified as interesting chemical groups for the design of new antifungal compounds. The compounds inhibited ICL of the dimorphic fungus P. brasiliensis activity. The compound 4559339 presented minimum inhibitory concentration of 7.3 µg/ml in P. brasiliensis with fungicidal effect at this concentration. Thus, a new potential antifungal against P. brasiliensis is proposed.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Paracoccidioides
/
Isocitrate Lyase
/
Antifungal Agents
Type of study:
Diagnostic_studies
Limits:
Animals
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Future Microbiol
Journal subject:
MICROBIOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Brazil