Michelle F. Paguio

TL;DR: The development of a new SYBR Green I-based plate assay for analyzing the activities of antimalarial drugs against intraerythrocytic Plasmodium falciparum significantly improves the pace at which antimalaria drug discovery efforts may proceed.

TL;DR: A refined model for altered CQ accumulation in CQR malarial parasites is proposed, wherein PfCRT catalyzes electrochemically downhill diffusion of NBD-CQ out of the DV, in response to DeltaPsi or DeltapH, at a rate that can partially compete with the ATP-dependent uptake of N BD-Cq by CQS parasites described in the previous paper.

TL;DR: Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD(50) doses, it is found reduced C Q accumulation is not the underlying cause of CQ R.

TL;DR: Several perfluorophenyl azido CQ analogues are designed and synthesized for PfCRT photolabeling studies and a model for a single CQ binding site in the Pf CRT protein is proposed.

TL;DR: The data show that an unusual autophagy – like process is either activated or inhibited for intraerythrocytic trophozoite parasites at LD50 doses (but not IC50 doses) of CQ, that the pathway is altered in CQR P. falciparum, and that it may contribute along with mutations in PfCRT to confer the C QRCC phenotype.