Synthesis and Antimalarial Activity of 4-Methylaminoquinoline Compounds against Drug-Resistant Parasite

This work describes the first total synthesis of mortiamides and their anti-malarial activity against a multi-drug resistant strain of Plasmodium falciparum.

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Blood schizontocidal activity of azithromycin and its combination with α/β arteether against multi-drug resistant Plasmodium yoelii nigeriensis, a novel MDR parasite model for antimalarial screening

Parasitology ◽

10.1017/s003118200500778x ◽

2005 ◽

Vol 131 (3) ◽

pp. 295-301 ◽

Cited By ~ 3

Author(s):

R. TRIPATHI ◽

S. DHAWAN ◽

G. P. DUTTA

Keyword(s):

Antimalarial Activity ◽

Wide Spectrum ◽

Oral Route ◽

Plasmodium Yoelii ◽

Drug Resistant ◽

Curative Effect ◽

Resistant Lines ◽

High Doses ◽

New Compounds

Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50–100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.

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Malagashanine potentiates chloroquine antimalarial activity in drug resistant Plasmodium malaria by modifying both its efflux and influx

Molecular and Biochemical Parasitology ◽

10.1016/j.molbiopara.2005.10.018 ◽

2006 ◽

Vol 146 (1) ◽

pp. 58-67 ◽

Cited By ~ 15

Author(s):

David Ramanitrahasimbola ◽

Philippe Rasoanaivo ◽

Suzanne Ratsimamanga ◽

Henri Vial

Keyword(s):

Antimalarial Activity ◽

Drug Resistant

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Metabolomic analysis of protozoan parasites

Microbiology Australia ◽

10.1071/ma11144 ◽

2011 ◽

Vol 32 (4) ◽

pp. 144

Author(s):

Eleanor Saunders ◽

David De Souza ◽

James McRae ◽

Vladimir Likic ◽

Malcolm McConville

Keyword(s):

Drug Targets ◽

Metabolic Networks ◽

Host Responses ◽

Drug Resistant ◽

Metabolomic Analysis ◽

Protozoan Parasites ◽

Metabolic Capacity ◽

Omics Technologies ◽

Potential Drug Targets ◽

Drug Resistant Parasite

Protozoan parasites cause a number of important diseases in humans, including malaria, African trypanosomiasis, Chagas disease and the leishmaniases. Current therapeutics for these diseases are limited and their effectiveness is being further undermined by the emergence of drug-resistant parasite strains. Parasite genome sequencing projects have provided new insights into the metabolic capacity of these pathogens and have highlighted potential drug targets. However, these genome-based reconstructions of metabolic networks are incomplete and we still have only a limited understanding of the metabolic requirements of these pathogens during infection. Metabolomics has emerged as a powerful new tool for investigating parasite metabolism and host responses, complementing more established omics technologies as well as being useful as a stand-alone technique.

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Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

Medicinal Research Reviews ◽

10.1002/med.21643 ◽

2019 ◽

Vol 40 (3) ◽

pp. 931-971 ◽

Cited By ~ 12

Author(s):

Lian‐Shun Feng ◽

Zhi Xu ◽

Le Chang ◽

Chuan Li ◽

Xiao‐Fei Yan ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Drug Resistant ◽

Hybrid Molecules

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Antimalarial activity of novel 4-aminoquinolines active against drug resistant strains

Bioorganic Chemistry ◽

10.1016/j.bioorg.2016.11.010 ◽

2017 ◽

Vol 70 ◽

pp. 74-85 ◽

Cited By ~ 10

Author(s):

Srinivasarao Kondaparla ◽

Awakash Soni ◽

Ashan Manhas ◽

Kumkum Srivastava ◽

Sunil K. Puri ◽

...

Keyword(s):

Antimalarial Activity ◽

Drug Resistant ◽

Resistant Strains ◽

Drug Resistant Strains

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ComparativeEx VivoActivity of Novel Endoperoxides in Multidrug-Resistant Plasmodium falciparum and P. vivax

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00283-12 ◽

2012 ◽

Vol 56 (10) ◽

pp. 5258-5263 ◽

Cited By ~ 33

Author(s):

Jutta Marfurt ◽

Ferryanto Chalfein ◽

Pak Prayoga ◽

Frans Wabiser ◽

Grennady Wirjanata ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Ex Vivo ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Intrinsic Activity ◽

Drug Resistant ◽

The Novel ◽

Content Type ◽

Artemisinin Derivatives

ABSTRACTThe declining efficacy of artemisinin derivatives againstPlasmodium falciparumhighlights the urgent need to identify alternative highly potent compounds for the treatment of malaria. In Papua Indonesia, where multidrug resistance has been documented against bothP. falciparumandP. vivaxmalaria, comparativeex vivoantimalarial activity againstPlasmodiumisolates was assessed for the artemisinin derivatives artesunate (AS) and dihydroartemisinin (DHA), the synthetic peroxides OZ277 and OZ439, the semisynthetic 10-alkylaminoartemisinin derivatives artemisone and artemiside, and the conventional antimalarial drugs chloroquine (CQ), amodiaquine (AQ), and piperaquine (PIP).Ex vivodrug susceptibility was assessed in 46 field isolates (25P. falciparumand 21P. vivax). The novel endoperoxide compounds exhibited potentex vivoactivity against both species, but significant differences in intrinsic activity were observed. Compared to AS and its active metabolite DHA, all the novel compounds showed lower or equal 50% inhibitory concentrations (IC50s) in both species (median IC50s between 1.9 and 3.6 nM inP. falciparumand 0.7 and 4.6 nM inP. vivax). The antiplasmodial activity of novel endoperoxides showed different cross-susceptibility patterns in the twoPlasmodiumspecies: whereas theirex vivoactivity correlated positively with CQ, PIP, AS, and DHA inP. falciparum, the same was not apparent inP. vivax. The current study demonstrates for the first time potent activity of novel endoperoxides against drug-resistantP. vivax. The high activity against drug-resistant strains of bothPlasmodiumspecies confirms these compounds to be promising candidates for future artemisinin-based combination therapy (ACT) regimens in regions of coendemicity.

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