In vitro and in vivo antimalarial activity of amphiphilic naphthothiazolium salts with amine-bearing side chains

Peter Ulrich, Gregory R. Gipson, Martha A. Clark, Abhai Tripathi, David J Sullivan, Carla Cerami

Research output: Contribution to journalArticle

Abstract

Because of emerging resistance to existing drugs, new chemical classes of antimalarial drugs are urgently needed. We have rationally designed a library of compounds that were predicted to accumulate in the digestive vacuole and then decrystallize hemozoin by breaking the iron carboxylate bond in hemozoin. We report the synthesis of 16 naphthothiazolium salts with amine-bearing side chains and their activities against the erythrocytic stage of Plasmodium falciparum in vitro. KSWI-855, the compound with the highest efficacy against the asexual stages of P. falciparum in vitro, also had in vitro activity against P. falciparum gametocytes and in vivo activity against P. berghei in a murinemalaria model.

Original languageEnglish (US)
Pages (from-to)824-832
Number of pages9
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume91
Issue number4
DOIs
StatePublished - Oct 1 2014

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Antimalarials
Plasmodium falciparum
Amines
Salts
Vacuoles
Iron
Pharmaceutical Preparations
In Vitro Techniques
hemozoin

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology
  • Medicine(all)

Cite this

In vitro and in vivo antimalarial activity of amphiphilic naphthothiazolium salts with amine-bearing side chains. / Ulrich, Peter; Gipson, Gregory R.; Clark, Martha A.; Tripathi, Abhai; Sullivan, David J; Cerami, Carla.

In: American Journal of Tropical Medicine and Hygiene, Vol. 91, No. 4, 01.10.2014, p. 824-832.

Research output: Contribution to journalArticle

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