Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria. Heidebrecht, R. W., Mulrooney, C., Austin, C. P., Barker, R. H., Beaudoin, J. A., Cheng, K. C., Comer, E., Dandapani, S., Dick, J., Duvall, J. R., Ekland, E. H., Fidock, D. A., Fitzgerald, M. E., Foley, M., Guha, R., Hinkson, P., Kramer, M., Lukens, A. K., Masi, D., Marcaurelle, L. A., Su, X., Thomas, C. J., We\̈iwer, M., Wiegand, R. C., Wirth, D., Xia, M., Yuan, J., Zhao, J., Palmer, M., Munoz, B., & Schreiber, S. ACS Med.~Chem.~Lett., 3(2):112--117, 2012. ![Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure--activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.
@article{Heidebrecht:2012fk,
Abstract = {Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure--activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.},
Author = {Heidebrecht, Richard W. and Mulrooney, Carol and Austin, Christopher P. and Barker, Robert H. and Beaudoin, Jennifer A. and Cheng, Ken Chih-Chien and Comer, Eamon and Dandapani, Sivaraman and Dick, Justin and Duvall, Jeremy R. and Ekland, Eric H. and Fidock, David A. and Fitzgerald, Mark E. and Foley, Michael and Guha, Rajarshi and Hinkson, Paul and Kramer, Martin and Lukens, Amanda K. and Masi, Daniela and Marcaurelle, Lisa A. and Su, Xin-Zhuan and Thomas, Craig J. and We{\"\i}wer, Michel and Wiegand, Roger C. and Wirth, Dyann and Xia, Menghang and Yuan, Jing and Zhao, Jinghua and Palmer, Michelle and Munoz, Benito and Schreiber, Stuart},
Date-Added = {2012-02-13 15:08:54 -0500},
Date-Modified = {2012-09-17 08:21:46 -0400},
Doi = {10.1021/ml200244k},
Eprint = {http://pubs.acs.org/doi/pdf/10.1021/ml200244k},
Journal = {{ACS} Med.~Chem.~Lett.},
Number = {2},
Pages = {112--117},
Title = {Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria},
Url = {http://pubs.acs.org/doi/abs/10.1021/ml200244k},
Volume = {3},
Year = {2012},
Bdsk-Url-1 = {http://pubs.acs.org/doi/abs/10.1021/ml200244k},
Bdsk-Url-2 = {http://dx.doi.org/10.1021/ml200244k}}
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