Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas

Kekeli Ekoue-Kovi, Kimberly Yearick, Daniel P. Iwaniuk, Jayakumar K. Natarajan, John Alumasa, Angel C. de Dios, Paul D. Roepe, Christian Wolf

Research output: Contribution to journalArticle

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Abstract

We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3-8 and 11-26, ureas 19-22, thioureas 23-26, and amides 27-54. Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of Plasmodium falciparum) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance. In particular, sulfonamide 3 exhibiting a short side chain with a terminal dansyl moiety combined high antiplasmodial potency with a low resistance index and showed IC50s of 17.5 and 22.7 nM against HB3 and Dd2 parasites.

Original languageEnglish (US)
Pages (from-to)270-283
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2009

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Thiourea
Sulfonamides
Chloroquine
Antimalarials
Amides
Urea
Plasmodium falciparum
Chain length
Parasites
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ekoue-Kovi, Kekeli ; Yearick, Kimberly ; Iwaniuk, Daniel P. ; Natarajan, Jayakumar K. ; Alumasa, John ; de Dios, Angel C. ; Roepe, Paul D. ; Wolf, Christian. / Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 1. pp. 270-283.
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Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas. / Ekoue-Kovi, Kekeli; Yearick, Kimberly; Iwaniuk, Daniel P.; Natarajan, Jayakumar K.; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 1, 01.01.2009, p. 270-283.

Research output: Contribution to journalArticle

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AU - Ekoue-Kovi, Kekeli

AU - Yearick, Kimberly

AU - Iwaniuk, Daniel P.

AU - Natarajan, Jayakumar K.

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