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.
TY - JOUR
AU - Konstantinović, Jelena
AU - Videnović, Milica
AU - Srbljanović, Jelena
AU - Đurković-Đaković, Olgica
AU - Bogojević, Katarina
AU - Sciotti, Richard J.
AU - Šolaja, Bogdan
PY - 2017
UR - http://rimi.imi.bg.ac.rs/handle/123456789/803
AB - 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 contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains.
PB - MDPI, Basel
T2 - Molecules
T1 - Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners
IS - 3
SP - 343
VL - 22
DO - 10.3390/molecules22030343
ER -
@article{
author = "Konstantinović, Jelena and Videnović, Milica and Srbljanović, Jelena and Đurković-Đaković, Olgica and Bogojević, Katarina and Sciotti, Richard J. and Šolaja, Bogdan",
year = "2017",
abstract = "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 contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners",
number = "3",
pages = "343",
volume = "22",
doi = "10.3390/molecules22030343"
}
Konstantinović, J., Videnović, M., Srbljanović, J., Đurković-Đaković, O., Bogojević, K., Sciotti, R. J.,& Šolaja, B.. (2017). Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners. in Molecules
MDPI, Basel., 22(3), 343.
https://doi.org/10.3390/molecules22030343
Konstantinović J, Videnović M, Srbljanović J, Đurković-Đaković O, Bogojević K, Sciotti RJ, Šolaja B. Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners. in Molecules. 2017;22(3):343.
doi:10.3390/molecules22030343 .
Konstantinović, Jelena, Videnović, Milica, Srbljanović, Jelena, Đurković-Đaković, Olgica, Bogojević, Katarina, Sciotti, Richard J., Šolaja, Bogdan, "Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners" in Molecules, 22, no. 3 (2017):343,
https://doi.org/10.3390/molecules22030343 . .
