Fast-Acting Chalcogen-Phosphoranes Inhibit Sensitive and Resistant Plasmodium falciparum Strains
Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Malaria remains a major global health challenge with growing resistance to current antimalarial drugs. In this study, we report the antiplasmodial activity of eight sulfur-containing chalcogen-phosphorane analogues that show submicromolar potency against Plasmodium falciparum 3D7 strain (IC 50 s = 0.7–1.9 μM) and reasonable selectivity indexes (SI) over HepG2 and HEK293 cells (SI ≥ 12). Electron-withdrawing substituents on the aromatic ring improved potency by two- to 3-fold. Compound 5, a representative compound of the series, showed fast-acting inhibitory activity that rapidly induced pyknotic nuclei, demonstrated no cross-resistance with standard antimalarials, and exhibited an additive interaction with artesunate. Stage-specific assays revealed pronounced activity against ring and trophozoite stages but reduced efficacy against schizonts, with longer exposure needed for maximal effects. In a murine Plasmodium berghei model, compound 5 showed modest in vivo activity but slightly improved the survival rate. These findings suggest that sulfur-containing chalcogen-phosphoranes represent an attractive series for hit-to-lead development.
Source: ACS Omega
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,935
Awards: The role of Chemistry in holobiont adaptation, G1478283260, G1520612187, Integrated investigation of inhibitors active on infectious diseases: insights into molecular and cellular mechanisms of function, CIBFar - Center for Innovation in Biodiversity and Drug Discovery, G221048998, G22113365, G2549540120, G295657101, G3252153558, G3690646728, G407438531, Identification of new antimalarial compounds: a multidisciplinary strategy aimed to search for potent chemical classes against new molecular targets and different stages of life of Plasmodium spp, G53628493, G5810920950, G6438247056, G6612846863, G6756993358, G6822879463, G921558302
OpenAlex ID: W7118583169