Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity.
ACS Med Chem Lett
; 11(7): 1450-1456, 2020 Jul 09.
Article
in En
| MEDLINE
| ID: mdl-32676153
ABSTRACT
Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacin-based hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 ± 1.2 nM and 25.52 ± 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 µM and 1 µM, respectively.
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1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2020
Document type:
Article
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