Antimalarial dyes revisited

Xanthenes, azines, oxazines and thiazines

Jonathan L Vennerstrom, M. T. Makler, C. K. Angerhofer, J. A. Williams

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

In 1891 Guttmann and Ehrlich (P. Guttmann and P. Ehrlich, Berlin Klin., Wochenschr. 28:953-956, 1891) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue. Since that time, sporadic reports of the antimalarial properties of several xanthene and azine dyes related to methylene blue have been noted. We report here the results from a reexamination of the antimalarial properties of methylene blue, Janus green B, and three rhodamine dyes and disclose new antimalarial data for 16 commercially available structural analogs of these dyes. The 50% inhibitory concentrations for the chloroquine-susceptible D6 clone and SN isolate and the chloroquine-resistant W2 clone of Plasmodium falciparum were determined by the recently described parasite lactate dehydrogenase enzyme assay. No cross-resistance to chloroquine was observed for any of the dyes. For the 21 dyes tested, no correlation was observed between antimalarial activity and cytotoxicity against KB cells. No correlation between log P (where P is the octanol/water partition coefficient) or relative catalyst efficiency for glucose oxidation and antimalarial activity or cytotoxicity was observed for the dyes as a whole or for the thiazine dyes. The thiazine dyes were the most uniformly potent structural class tested, and among the dyes in this class, methylene blue was notable for both its high antimalarial potency and selectivity.

Original languageEnglish (US)
Pages (from-to)2671-2677
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume39
Issue number12
DOIs
StatePublished - Jan 1 1995

Fingerprint

Xanthenes
Thiazines
Oxazines
Antimalarials
Coloring Agents
Methylene Blue
Chloroquine
Clone Cells
KB Cells
Octanols
Rhodamines
Enzyme Assays
Berlin
Plasmodium falciparum
L-Lactate Dehydrogenase
Inhibitory Concentration 50
Oral Administration
Parasites

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Antimalarial dyes revisited : Xanthenes, azines, oxazines and thiazines. / Vennerstrom, Jonathan L; Makler, M. T.; Angerhofer, C. K.; Williams, J. A.

In: Antimicrobial Agents and Chemotherapy, Vol. 39, No. 12, 01.01.1995, p. 2671-2677.

Research output: Contribution to journalArticle

Vennerstrom, Jonathan L ; Makler, M. T. ; Angerhofer, C. K. ; Williams, J. A. / Antimalarial dyes revisited : Xanthenes, azines, oxazines and thiazines. In: Antimicrobial Agents and Chemotherapy. 1995 ; Vol. 39, No. 12. pp. 2671-2677.
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