Antimalarial and anticancer activities of artemisinin–quinoline hybrid-dimers and pharmacokinetic properties in mice

Lombard, Marli C.; N’Da, David D.; Breytenbach, Jaco C.; Kolesnikova, Natasha I.; Ba, Christophe Tran Van; Wein, Sharon; Norman, Jennifer; Denti, Paolo; Vial, Henri; Wiesner, Lubbe

doi:10.1016/j.ejps.2012.09.019

Cited by 37 publications

(31 citation statements)

References 27 publications

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“…5) have excellent potential as antimalarial drugs as they are active at the nanomolar range; importantly, very low parasitemia (o 1%) was observed after five days of treatment. Pharmacokinetic analysis suggested that the activity of these hybrids could be due to active metabolites, which was confirmed with in silico studies (Lombard et al, 2012).…”

Section: Learning From the Cq Hybrid Approach For Antimalarial Drug Dmentioning

confidence: 89%

“…Taking these two facts into consideration, Lambord et al synthesized hybrid molecules of CQ-artemisinin dimer. In this approach, the authors coupled 4-aminoquinolin-artemisisnin hybrids with another artemisinin unit to produce a hybrid with dual pharmacological functions (Lombard et al, 2012). Hybrids 14 and 15 shown in Fig.…”

Section: Cq-artemisinin Hybridsmentioning

confidence: 99%

“…Unfortunately, however, a pharmacokinetics study showed that these hybrids have very short half-life (8.54 and 5.33 min for hybrids 14 and 15, respectively) and showed very low oral volume distributions. Therefore, further structural modifications may be required to increase the bioavailability and half-life of these hybrids (Lombard et al, 2012).…”

Section: Cq-artemisinin Hybridsmentioning

confidence: 99%

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Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Srivastava

Lee

2015

European Journal of Pharmacology

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Section: Learning From the Cq Hybrid Approach For Antimalarial Drug Dmentioning

confidence: 89%

Section: Cq-artemisinin Hybridsmentioning

confidence: 99%

Section: Cq-artemisinin Hybridsmentioning

confidence: 99%

See 1 more Smart Citation

Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Srivastava

Lee

2015

European Journal of Pharmacology

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“…22 In a follow-up study by the same group, extra in vitro and in vivo antimalarial assessments of 11b and 11d have been performed. 23 The in vitro antiplasmodial activities of hybrid dimers 11b and 11d against CQS (3D7) strain of P. falciparum were 9 and 30 nM, respectively, which were equipotent as compared to CQ's activity of 20 nM. Furthermore, these dimers 11b and 11d…”

Section: Figurementioning

confidence: 95%

“…47 Interestingly, the hybrids with conformationally constrained aminopiperidine linkers also delivered potent K1 activity, which is in contrast with previously described CQ derivatives where acyclic linkers were more potent than constrained cyclic linker. [23][24] Furthermore, the hybrid analogs exhibited a good cytotoxicity profile and the in vivo antiplasmodial activity of compounds 35 and 36 against a…”

Section: Figure 14mentioning

confidence: 99%

Quinoline-based antimalarial hybrid compounds

Vandekerckhove

D’hooghe

2015

Bioorganic & Medicinal Chemistry

195

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Quinoline-containing compounds, such as quinine and chloroquine, have a long-standing history as potent antimalarial agents. However, the increasing resistance of the Plasmodium parasite against these drugs and the lack of licensed malaria vaccines have forced chemists to develop synthetic strategies toward novel biologically active molecules. A strategy that has attracted considerable attention in current medicinal chemistry is based on the conjugation of two biologically active molecules into one hybrid compound. Since quinolines are considered to be privileged antimalarial building blocks, the synthesis of quinoline-containing antimalarial hybrids has been elaborated extensively in recent years. This review provides a literature overview of antimalarial hybrid molecules containing a quinoline core, covering publications between 2009 and 2014.

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Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

Zhang

2019

Archiv der Pharmazie

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Anticancer agents play a pivotal role in cancer treatment. However, most of the anticancer drugs currently used in the clinics have a severe anticancer scenario, as well as low specificity and fatal side effects. Thus, there is an urgent demand to develop novel drugs with great efficacy, high specificity, and low side effects.Artemisinin and its semisynthetic derivatives are mainstays of chemotherapy against malaria, and artemisinin-based compounds, especially artemisinin-derived dimers, also exhibit excellent in vitro and in vivo anticancer activity. The structure-activity relationship (SAR) demonstrated that the linker between the two artemisinin moieties influenced the anticancer activity significantly; so, the rational design of the linker may provide valuable therapeutic intervention for the treatment of cancer.This review outlines the potential anticancer activity of artemisinin-derived dimers tethered by different linkers. The SARs, as well as mechanisms of action, are discussed to provide insights for the rational design of more effective dimers.

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Antimalarial and anticancer activities of artemisinin–quinoline hybrid-dimers and pharmacokinetic properties in mice

Cited by 37 publications

References 27 publications

Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Quinoline-based antimalarial hybrid compounds

Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

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