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041			_aeng
100			_92238 _aAzcárate, Isabel G. _eInstituto de Investigación imas12
100			_91902 _aBautista, José M. _eInstituto de Investigación i+12
245	0	0	_aAnalogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo. _h[artículo]
260			_bProceedings of the National Academy of Sciences of the United States of America, _c2014
300			_a111(51):E5508-17.
500			_aFormato Vancouver: Novoa EM, Camacho N, Tor A, Wilkinson B, Moss S, Marín-García P et al. Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5508-17.
501			_aPMID: 25489076 PMC4280603
504			_aContiene 71 referencias
520			_aMalaria remains a major global health problem. Emerging resistance to existing antimalarial drugs drives the search for new antimalarials, and protein translation is a promising pathway to target. Here we explore the potential of the aminoacyl-tRNA synthetase (ARS) family as a source of antimalarial drug targets. First, a battery of known and novel ARS inhibitors was tested against Plasmodium falciparum cultures, and their activities were compared. Borrelidin, a natural inhibitor of threonyl-tRNA synthetase (ThrRS), stands out for its potent antimalarial effect. However, it also inhibits human ThrRS and is highly toxic to human cells. To circumvent this problem, we tested a library of bioengineered and semisynthetic borrelidin analogs for their antimalarial activity and toxicity. We found that some analogs effectively lose their toxicity against human cells while retaining a potent antiparasitic activity both in vitro and in vivo and cleared malaria from Plasmodium yoelii-infected mice, resulting in 100% mice survival rates. Our work identifies borrelidin analogs as potent, selective, and unexplored scaffolds that efficiently clear malaria both in vitro and in vivo.
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280603/ _yAcceso libre
942			_2ddc _cART _n0