Antimalarials

Smithson, David C.; Guiguemde, W. Armand; Guy, R. Kiplin

doi:10.1002/0471266949.bmc234

Cited by 6 publications

(3 citation statements)

References 797 publications

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“…In a recent review, we estimated that there are fewer than 30 small molecule scaffolds with bona fide in vivo activity against P. falciparum (Smithson, et al, 2010). Even among the examples that are active in vivo , only a small number prove themselves in clinical development – with the number of distinct antimalarial chemotypes in the clinic being fewer than 10 (Table 1).…”

Section: Biologymentioning

confidence: 99%

Global Phenotypic Screening for Antimalarials

Guiguemde

Shelat

Garcia-Bustos

et al. 2012

Chemistry & Biology

131

119

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Malaria, a devastating infectious disease caused by Plasmodium spp., leads to roughly 655,000 deaths per year, mostly of African children. To compound the problem, drug resistance has emerged to all classical antimalarials and may be emerging for artemisinin-based combination therapies. To address the need for new antimalarials with novel mechanisms, several groups carried out phenotypic screening campaigns to identify compounds inhibiting growth of the blood stages of Plasmodium falciparum. In this review, we describe the characterization of these compounds, explore currently ongoing strategies to develop lead molecules, and endorse the concept of a “malaria box” of publicly accessible active compounds.

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Section: Biologymentioning

confidence: 99%

Global Phenotypic Screening for Antimalarials

Guiguemde

Shelat

Garcia-Bustos

et al. 2012

Chemistry & Biology

131

119

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“…In the past, all antimalarial agents that have been deployed for the treatment of malaria, e.g. quinine, chloroquine, amodiaquine, sulfadoxine-pyrimethamine, mefloquine, piperaquine and halofantrine, shared the same fate [ 1 , [4] , [5] , [6] ]. Plasmodium parasites developed clinical resistance to these antiplasmodials in one area and then spread to other parts of the world [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

Walle

Boone

Puyvelde

et al. 2020

European Journal of Medicinal Chemistry

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The parasitic disease malaria places almost half of the world’s population at risk of infection and is responsible for more than 400,000 deaths each year. The first-line treatment, artemisinin combination therapies (ACT) regimen, is under threat due to emerging resistance of Plasmodium falciparum strains in e.g. the Mekong delta. Therefore, the development of new antimalarial agents is crucial in order to circumvent the growing resistance. Chloroquine, the long-established antimalarial drug, still serves as model compound for the design of new quinoline analogues, resulting in numerous new active derivatives against chloroquine-resistant P. falciparum strains over the past twenty years. In this work, a set of functionalized quinoline analogues, decorated with a modified piperidine-containing side chain, was synthesized. Both amino- and (aminomethyl)quinolines were prepared, resulting in a total of 18 novel quinoline-piperidine conjugates representing four different chemical series. Evaluation of their in vitro antiplasmodium activity against a CQ-sensitive (NF54) and a CQ-resistant (K1) strain of P. falciparum unveiled highly potent activities in the nanomolar range against both strains for five 4-aminoquinoline derivatives. Moreover, no cytotoxicity was observed for all active compounds at the maximum concentration tested. These five new aminoquinoline hit structures are therefore of considerable value for antimalarial research and have the potency to be transformed into novel antimalarial agents upon further hit-to-lead optimization studies.

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“…It is also highly desirable for antimalarials to display exoerythrocytic activity, which includes activity toward the sexual (gametocyte) and liver (especially hypnozoite) stages of the parasite life cycle to provide transmission-blocking and prophylactic activity, respectively. Following our previous review of known antimalarials and other antimalarial reviews, in this review we seek to outline chemotypes currently in clinical development for the treatment of malaria.…”

Section: Introductionmentioning

confidence: 99%