Fig. 5. Transmission-blocking activity of active compounds from the PRB against P. falciparum stage IV/V gametocytes, gametes and oocysts.
a Chemical cluster analysis of the gametocyte hit compounds, using the FragFP descriptor and a Tanimoto similarity index >0.50 in OSIRIS DataWarrior v 5.0.0, and network construction with Cytoscape v 3.7.2. Edges were assigned between similar scaffolds and a parent node. Active compounds with IC50 values <2 µM are indicated in green, those with additional activity at the same cut-off on ABS are indicated with hexagons and those with shared activity on liver stages with black borders. Structures are highlighted for selected compounds. Data are from three independent biological repeats (n = 3), each performed in technical triplicates, ±S.E. b Nineteen compounds with activity against P. falciparum stage IV/V gametocytes were evaluated for their ability to inhibit male gamete exflagellation. Compounds (2 µM) were used on stage IV/V gametocytes for a 48-h treatment prior to inducing male gamete exflagellation (carry-over format). Data are from three independent biological repeats (n = 3), performed in technical triplicates, mean ± S.E indicated, except for MMV1633967, MMV1634399 and MMV000043, for which data are from n = 2 biological repeats). Individual data points are indicated in symbols. c SMFA data for 17 compounds (selected based on >50% inhibition on male gamete exflagellation). SMFA was performed by feeding A. coluzzii mosquitoes with compound-treated gametocyte cultures (48 h treatment at 2 µM). Data are presented as percentage of TRA (transmission-reducing activity, reduction in oocyst intensity: , where i: oocyst number (intensity), C: control and T: treated) from at least three independent biological repeats (n = 4), performed with technical duplicates, mean ± S.E indicated. Individual data points are indicated in symbols.