Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides,sulfonamides, ureas and thioureas |
| |
Authors: | Kekeli Ekoue-Kovi Kimberly Yearick Daniel P. Iwaniuk Jayakumar K. Natarajan John Alumasa Angel C. de Dios Paul D. Roepe Christian Wolf |
| |
Affiliation: | 1. Department of Chemistry, Georgetown University, 37th and “O” Streets, Washington, DC 20057, USA;2. Department of Biochemistry and Cellular and Molecular Biology, Georgetown University, 37th and “O” Streets, Washington, DC 20057, USA;3. Center for Infectious Diseases, Georgetown University, 37th and “O” Streets, Washington, DC 20057, USA |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|