Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity

Mynthia Cabrera; Michelle F. Paguio; Changan Xie; Paul D. Roepe

doi:10.1021/bi901765v

Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity

Mynthia Cabrera
, Michelle F. Paguio
, Changan Xie
, Paul D. Roepe

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Chloroquine (CQ) accumulation studies in live malaria parasites are typically conducted at low nanomolar CQ concentrations, and definition of CQ resistance (CQR) has been via growth inhibition assays versus low-dose CQ (i.e., via IC₅₀ ratios). These data have led to the nearly universally accepted idea that reduced parasite CQ accumulation is the underlying basis of CQR. Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD₅₀ doses, we find reduced CQ accumulation is not the underlying cause of CQR.

Original language	English (US)
Pages (from-to)	11152-11154
Number of pages	3
Journal	Biochemistry
Volume	48
Issue number	47
DOIs	https://doi.org/10.1021/bi901765v
State	Published - Dec 1 2009

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Biochemistry

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10.1021/bi901765v

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title = "Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity",

abstract = "Chloroquine (CQ) accumulation studies in live malaria parasites are typically conducted at low nanomolar CQ concentrations, and definition of CQ resistance (CQR) has been via growth inhibition assays versus low-dose CQ (i.e., via IC50 ratios). These data have led to the nearly universally accepted idea that reduced parasite CQ accumulation is the underlying basis of CQR. Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD50 doses, we find reduced CQ accumulation is not the underlying cause of CQR.",

author = "Mynthia Cabrera and Paguio, \{Michelle F.\} and Changan Xie and Roepe, \{Paul D.\}",

year = "2009",

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language = "English (US)",

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T1 - Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity

AU - Cabrera, Mynthia

AU - Paguio, Michelle F.

AU - Xie, Changan

AU - Roepe, Paul D.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Chloroquine (CQ) accumulation studies in live malaria parasites are typically conducted at low nanomolar CQ concentrations, and definition of CQ resistance (CQR) has been via growth inhibition assays versus low-dose CQ (i.e., via IC50 ratios). These data have led to the nearly universally accepted idea that reduced parasite CQ accumulation is the underlying basis of CQR. Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD50 doses, we find reduced CQ accumulation is not the underlying cause of CQR.

AB - Chloroquine (CQ) accumulation studies in live malaria parasites are typically conducted at low nanomolar CQ concentrations, and definition of CQ resistance (CQR) has been via growth inhibition assays versus low-dose CQ (i.e., via IC50 ratios). These data have led to the nearly universally accepted idea that reduced parasite CQ accumulation is the underlying basis of CQR. Surprisingly, when quantifying CQR via cytocidal CQ activity and examining CQ accumulation at medically relevant LD50 doses, we find reduced CQ accumulation is not the underlying cause of CQR.

UR - https://www.scopus.com/pages/publications/72749090340

UR - https://www.scopus.com/pages/publications/72749090340#tab=citedBy

U2 - 10.1021/bi901765v

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EP - 11154

JO - Biochemistry

JF - Biochemistry

IS - 47

ER -

Reduced digestive vacuolar accumulation of chloroquine is not linked to resistance to chloroquine toxicity

Abstract

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