The Price of Success

White, Elise; Chambers, Veronica; hooks, bell

doi:10.2307/4024276

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“…Unfortunately, endoperoxides are ineffective in the liver stage, and there are concerns that tolerance to artemisinins may be emerging in Cambodia. 5 There is a real and immediate need to discover new drugs which possess activity against both liver and blood stage malaria parasites.…”

mentioning

confidence: 99%

The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment

Saint-Léger¹,

Sinadinos²,

Pouplana

2016

Bioengineered

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Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes.

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confidence: 99%