Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners
AuthorsKonstantinović, Jelena M.
Šolaja, Bogdan A.
Article (Published version)
MetadataShow full item record
Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC50 = 6 nM, and cured 5/5 Plasmodium berghei infected mice when dosed orally at 160 mg/kg/day x 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of lt 1. This is in sharp cont...rast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains.
Keywords:antimalarials / thiophene / benzothiophene / aminoquinoline
Source:Molecules, 2017, 22, 3
- Mdpi Ag, Basel
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Control of infections by Apicomplexan pathogens: from novel drug targets to prediction (RS-41019)
- Serbian Academy of Sciences and Arts
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3022