Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin-4- yl)heteroalkanediamines

Jonathan L. Vennerstrom, Arba L. Ager, Arnulf Dorn, Steven L. Andersen, Lucia Gerena, Robert G. Ridley, Wilbur K. Milhous

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

N,N-Bis(7-chloroquinolin-4-yl)heteroalkanediamines 1-11 were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. These bisquinolines had IC50 values from 1 to 100 nM against P. falciparum in vitro. Six of the 11 bisquinolines were significantly more potent against the chloroquine-resistant W2 clone compared to the chloroquine-sensitive D6 clone. For bisquinolines 1-11 there was no relationship between the length of the bisquinoline heteroalkane bridge and antimalarial activity and no correlation between in vitro and in vivo antimalarial activities. Bisquinolines with alkyl ether and piperazine bridges were substantially more effective than bisquinolines with alkylamine bridges against P. berghei in vivo. Bisquinolines 1-10 were potent inhibitors of hematin polymerization with IC50 values falling in the narrow range of 5-20 μM, and there was a correlation between potency of inhibition of hematin polymerization and inhibition of parasite growth. Compared to alkane- bridged bisquinolines (Vennerstrom et al., 1992), none of these heteroalkane- bridged bisquinolines had sufficient antimalarial activity to warrant further investigation of the series.

Original languageEnglish (US)
Pages (from-to)4360-4364
Number of pages5
JournalJournal of Medicinal Chemistry
Volume41
Issue number22
DOIs
StatePublished - Oct 23 1998

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Antimalarials
Plasmodium berghei
Hemin
Chloroquine
Plasmodium falciparum
Polymerization
Inhibitory Concentration 50
Clone Cells
Alkanes
Ether
Parasites
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Vennerstrom, J. L., Ager, A. L., Dorn, A., Andersen, S. L., Gerena, L., Ridley, R. G., & Milhous, W. K. (1998). Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin-4- yl)heteroalkanediamines. Journal of Medicinal Chemistry, 41(22), 4360-4364. https://doi.org/10.1021/jm9803828

Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin-4- yl)heteroalkanediamines. / Vennerstrom, Jonathan L.; Ager, Arba L.; Dorn, Arnulf; Andersen, Steven L.; Gerena, Lucia; Ridley, Robert G.; Milhous, Wilbur K.

In: Journal of Medicinal Chemistry, Vol. 41, No. 22, 23.10.1998, p. 4360-4364.

Research output: Contribution to journalArticle

Vennerstrom, JL, Ager, AL, Dorn, A, Andersen, SL, Gerena, L, Ridley, RG & Milhous, WK 1998, 'Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin-4- yl)heteroalkanediamines', Journal of Medicinal Chemistry, vol. 41, no. 22, pp. 4360-4364. https://doi.org/10.1021/jm9803828
Vennerstrom, Jonathan L. ; Ager, Arba L. ; Dorn, Arnulf ; Andersen, Steven L. ; Gerena, Lucia ; Ridley, Robert G. ; Milhous, Wilbur K. / Bisquinolines. 2. Antimalarial N,N-Bis(7-chloroquinolin-4- yl)heteroalkanediamines. In: Journal of Medicinal Chemistry. 1998 ; Vol. 41, No. 22. pp. 4360-4364.
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