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Antileishmanial activity evaluation of a natural amide and its synthetic analogs against Leishmania (V.) braziliensis: an integrated approach in vitro and in silico
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2021
-
Abstract
- Leishmaniasis is considered a neglected disease, which makes it an unattractive market for the pharmaceutical industry; hence, efforts in the search for biologically active substances are hampered by this lack of financial motivation. Thus, in the present study, we report the leishmanicidal activity and the possible mechanisms of action of compounds with promising activity against the species Leishmania (V.) braziliensis, the causative agent of the skin disease leishmaniasis. The natural compound 1a (piplartine) and the analog 2a were the most potent against promastigote forms with growth inhibition values for 50% of the parasite population (IC50) = 8.58 and 11.25 μM, respectively. For amastigote forms, the ICa50 values were 1.46 and 16.7 μM, respectively. In the molecular docking study, piplartine showed favorable binding energy (-7.13 kcal/mol) and with 50% inhibition of trypanothione reductase (IC50) = 91.1 μM. Preliminary investigations of the mechanism of action indicate that piplartine increased ROS levels, induced loss of cell membrane integrity, and caused accumulation of lipid bodies after 24 h of incubation at its lowest effective concentration (IC50), which was not observed for the synthetic analog 2a. The mode of action for the leishmanicidal activity of piplartine (1a) was assigned to involve affinity for the trypanothione reductase of Leishmania (V.) braziliensis TR.
- Subjects :
- In silico
Population
Biology
Leishmania braziliensis
chemistry.chemical_compound
Cell Line, Tumor
Chlorocebus aethiops
medicine
Animals
Humans
Computer Simulation
NADH, NADPH Oxidoreductases
education
Amastigote
Vero Cells
IC50
Piperidones
education.field_of_study
General Veterinary
ANTIPROTOZOÁRIOS
General Medicine
Leishmania
biology.organism_classification
Amides
Trypanocidal Agents
In vitro
Molecular Docking Simulation
Infectious Diseases
Mechanism of action
chemistry
Biochemistry
Insect Science
Parasitology
medicine.symptom
Growth inhibition
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Accession number :
- edsair.doi.dedup.....fb8ed1bd14f8d76548074f50b0662bcf