Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound - Archive ouverte HAL Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Year : 2024

Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound

Abstract

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3′) and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying in vitro antiplasmodial activity similar to that of unmodified Hit A. This allowed us to identify the PfPYK-1 kinase and the PfRab6 GTP-ase as potential targets of Hit A.
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Year Month Jours
Avant la publication
Wednesday, August 28, 2024
Embargoed file
Wednesday, August 28, 2024
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hal-04503278 , version 1 (28-03-2024)

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Attribution - NonCommercial

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C. Kieffer, N. Primas, S. Hutter, A. Merckx, L. Reininger, et al.. Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound. Bioorganic and Medicinal Chemistry, 2024, 102, pp.117654. ⟨10.1016/j.bmc.2024.117654⟩. ⟨hal-04503278⟩
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