Antimalarial Efficacy of Hydroxyethylapoquinine (SN-119) and Its Derivatives

Sanders, Natalie G.; Meyers, David J.; Sullivan, David J.

doi:10.1128/aac.01704-13

Cited by 16 publications

(12 citation statements)

References 38 publications

(43 reference statements)

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“…Excepting atovaquone, all antimalarials tested demonstrated low toxicity in Vero cells (CC 50 ≥ 483.5 μM) (Table 1). Chloroquine, primaquine, quinine and tetracycline usually lead to toxicity in non-tumoral lineages at concentrations above 51 μM, 395 μM, 200 μM and 225 μM, respectively (Lelièvre et al, 2012;Davanço et al, 2014;Sanders et al, 2014;Ou at al., 2019). However, we must consider that the CC 50 concentrations vary depending on the cell lineage employed (Florento et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum

Pereira

Luca

Abichabki

et al. 2021

Rev. Bras. Parasitol. Vet.

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Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.

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Section: Resultsmentioning

confidence: 99%

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum

Pereira

Luca

Abichabki

et al. 2021

Rev. Bras. Parasitol. Vet.

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“…Quinine is mainly used for malaria [3]. Although artemisinin is used as a substitute for other antimalarials as the first-line drug in the treatment of malaria, quinine and/or quinidine are still widely used for treating severe malaria because of the lack of availability of intravenous artesunate [3,23,24]. However, cardiotoxicity has become a major adverse effect during treatment with quinidine and quinine [4,5].…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect

Meng

Fan

Shi

et al. 2016

IJMS

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Diastereoisomers of quinidine and quinine are used to treat arrhythmia and malaria, respectively. It has been reported that both drugs block the hERG (human ether-a-go-go-related gene) potassium channel which is essential for myocardium repolarization. Abnormality of repolarization increases risk of arrhythmia. The aim of our research is to study and compare the impacts of quinidine and quinine on hERG. Results show that both drugs block the hERG channel, with quinine 14-fold less potent than quinidine. In addition, they presented distinct impacts on channel dynamics. The results imply their stereospecific block effect on the hERG channel. However, F656C-hERG reversed this stereoselectivity. The mutation decreases affinity of the two drugs with hERG, and quinine was more potent than quinidine in F656C-hERG blockage. These data suggest that F656 residue contributes to the stereoselective pocket for quinidine and quinine. Further study demonstrates that both drugs do not change hERG protein levels. In rescue experiments, we found that they exert no reverse effect on pentamidine- or desipramine-induced hERG trafficking defect, although quinidine has been reported to rescue trafficking-deficient pore mutation hERG G601S based on the interaction with F656. Our research demonstrated stereoselective effects of quinidine and quinine on the hERG channel, and this is the first study to explore their reversal potency on drug-induced hERG deficiency.

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“…Hence, compound 11 seems to be an adequate lead for developing a new class of Q-based antimalarials, on which further chemical modifications should be pursued. 21 Finally, an example that emerged in line with two of the major 21st century keywords in antimalarial chemotherapy, artemisinin and covalent bitherapy: 22 Bell and co-workers created an artemisinin/quinine conjugate (12, Figure 5) through coupling of dihydroartemisinin to a carboxylic acid derivative of Q, via an ester linkage. 23 Hybrid compounds underlying the covalent bitherapy concept consist of a single molecule that joins together, through a covalent bond, two different pharmacological agents.…”

Section: Quinine: Past Present and Futurementioning

confidence: 99%