Hundreds of dual-stage antimalarial molecules discovered by a functional gametocyte screen.
Nat Commun
; 8: 15160, 2017 05 17.
Article
in En
| MEDLINE
| ID: mdl-28513586
ABSTRACT
Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2 µM, chemically classified into 57 clusters and 33 singletons. Up to 68% of the hits are chemotypes described for the first time as late-stage gametocyte-targeting molecules. In addition, the biological profile of 90 compounds representing the chemical diversity is assessed. We confirm in vitro transmission-blocking activity of four of the six selected molecules belonging to three distinct scaffold clusters. Overall, this TCAMS gametocyte screen provides 276 promising antimalarial molecules with dual asexual/sexual activity, representing starting points for target identification and candidate selection.
Full text:
1
Collection:
01-internacional
Health context:
3_ND
Database:
MEDLINE
Main subject:
Drug Evaluation, Preclinical
/
Germ Cells
/
Antimalarials
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Nat Commun
Year:
2017
Document type:
Article