|
Title
|
|
|
|
Antimalarial versus cytotoxic properties of dual drugs derived from 4-aminoquinolines and Mannich bases: interaction with DNA
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| The synthesis and biological evaluation of new organic and organometallic dual drugs designed as potential antimalarial agents are reported. A series of 4-aminoquinoline-based Mannich bases with variations in the aliphatic amino side chain were prepared via a three-steps synthesis. These compounds were also tested against chloroquine-susceptible and chloroquine-resistant strains of Plasmodium falciparum and assayed for their ability to inhibit the formation of β-hematin in vitro using a colorimetric β-hematin inhibition assay. Several compounds showed a marked antimalarial activity, with IC50 and IC90 values in the low nM range but also a high cytotoxicity against mammalian cells, in particular a highly drug-resistant glioblastoma cell line. The newly designed compounds revealed high DNA binding properties, especially for the GC-rich domains. Altogether, these dual drugs seem to be more appropriate to be developed as antiproliferative agents against mammalian cancer cells than Plasmodium parasites. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
| |
|
Publication
|
|
|
|
Washington, D.C.
:
2010
| |
|
ISSN
|
|
|
|
0022-2623
[print]
1520-4804
[online]
| |
|
DOI
|
|
|
|
10.1021/JM9018383
| |
|
Volume/pages
|
|
|
|
53
:8
(2010)
, p. 3214-3226
| |
|
ISI
|
|
|
|
000276562400019
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|