title: Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas.
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 IC(50)s of 17.5 and 22.7 nM against HB3 and Dd2 parasites.
authors.affiliation: Department of Chemistry, Georgetown University, 37th and "O" Streets, Washington, DC 20057, USA.
authors.forename: Kekeli
authors.initials: K
authors.lastname: Ekoue-Kovi
authors.forename: Kimberly
authors.initials: K
authors.lastname: Yearick
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Iwaniuk
authors.forename: Jayakumar K
authors.initials: JK
authors.lastname: Natarajan
authors.forename: John
authors.initials: J
authors.lastname: Alumasa
authors.forename: Angel C
authors.initials: AC
authors.lastname: de Dios
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
mesh_terms: D000577:Amides; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002738:Chloroquine / Q000031:analogs & derivatives*; D004351:Drug Resistance / Q000187:drug effects; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects*; D013449:Sulfonamides; D013890:Thiourea; D014508:Urea
chemical_list: D000577:Amides; D000962:Antimalarials; D013449:Sulfonamides; D002738:Chloroquine; D014508:Urea; D013890:Thiourea