Synthesis and structure–activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

Zhang, Yiqun; Guiguemde, W. Armand; Sigal, Martina; Zhu, Fangyi; Connelly, Michele; Nwaka, Solomon; Guy, R. Kiplin

doi:10.1016/j.bmc.2010.02.013

Cited by 40 publications

(42 citation statements)

References 34 publications

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“…9–11 We have previously reported the discovery of the 4(1H)-quinolones, which are structurally related to a class of antimalarial compounds known as the endochins. 12 …”

Section: Introductionmentioning

confidence: 99%

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

et al. 2012

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Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multi-drug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

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“…9–11 We have previously reported the discovery of the 4(1H)-quinolones, which are structurally related to a class of antimalarial compounds known as the endochins. 12 …”

Section: Introductionmentioning

confidence: 99%

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

et al. 2012

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“…Since the discovery of the anti-malarial activity of ICI56-780, a carboxyl derivative of quinolones [85], screening of new compounds has led to the discovery of various 3-carboxyquinolones, which displayed in vitro activity <100 nM against P. falciparum strains and targeted the cytochrome bc 1 complex and the dihydroorotate dehydrogenase (DHODH) [86, 87]. …”

Section: Anti-malarial Quinolonesmentioning

confidence: 99%

Antibiotics in malaria therapy: which antibiotics except tetracyclines and macrolides may be used against malaria?

Gaillard

Madamet

Tsombeng

et al. 2016

Malar J

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Malaria, a parasite vector-borne disease, is one of the most significant health threats in tropical regions, despite the availability of individual chemoprophylaxis. Malaria chemoprophylaxis and chemotherapy remain a major area of research, and new drug molecules are constantly being developed before drug-resistant parasites strains emerge. The use of anti-malarial drugs is challenged by contra-indications, the level of resistance of Plasmodium falciparum in endemic areas, clinical tolerance and financial cost. New therapeutic approaches are currently needed to fight against this disease. Some antibiotics that have shown potential effects on malaria parasite have been recently studied in vitro or in vivo intensively. Two families, tetracyclines and macrolides and their derivatives have been particularly studied in recent years. However, other less well-known have been tested or are being used for malaria treatment. Some of these belong to older families, such as quinolones, co-trimoxazole or fusidic acid, while others are new drug molecules such as tigecycline. These emerging antibiotics could be used to prevent malaria in the future. In this review, the authors overview the use of antibiotics for malaria treatment.

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“…A systematic approach including a methodical variation of sterics, electrostatics and hydrophobics following Topliss and Hansch analysis was applied to conduct the optimization. A meta-substituted aryl group at the C2 position was established to be extremely important for antimalarial activity [57]. In order to investigate this trend more precisely, more than 20 additional analogues were synthesized and tested in vitro (Figure 12).…”

Section: 3-ester-4(1h)-quinolonesmentioning

confidence: 99%

4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

Monastyrskyi¹,

Kyle²,

Manetsch³

2014

CTMC

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Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed.

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Synthesis and structure–activity relationships of antimalarial 4-oxo-3-carboxyl quinolones

Cited by 40 publications

References 34 publications

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

Lead Optimization of 3-Carboxyl-4(1H)-Quinolones to Deliver Orally Bioavailable Antimalarials

Antibiotics in malaria therapy: which antibiotics except tetracyclines and macrolides may be used against malaria?

4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

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