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Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A

  1. Author:
    Solaja, B. A.
    Opsenica, D.
    Smith, K. S.
    Milhous, W. K.
    Terzic, N.
    Opsenica, I.
    Burnett, J. C.
    Nuss, J.
    Gussio, R.
    Bavari, S.

  2. Author Address

    Solaja, Bogdan A.; Terzic, Natasa, Opsenica, Igor] Univ Belgrade, Fac Chem, Belgrade 11001, Serbia. [Opsenica, Dejan, Bavari, Sina] Inst Chem Technol & Met, Belgrade 11000, Serbia. [Smith, Kirsten S.; Milhous, Wilbur K.] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA. [Burnett, James C.] SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD USA. Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA. [Gussio, Rick] Natl Canc Inst, Dev Therapeut Program, Frederick, MD 21702 USA. [Nuss, Jon] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
    1. Year: 2008
  2. Journal: Journal of Medicinal Chemistry
    1. 51
    2. 15
    3. Pages: 4388-4391
  4. Type of Article: Article
  1. Abstract:

    We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.

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  2. DOI: 10.1021/jm800737y
  3. PMID: 18637666

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