Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease

ACS Medicinal Chemistry Letters

Volumn 5, Issue 2, 2014, Pages 149-153

  Dandapani, Sivaraman ^a   Germain, Andrew R ^a   Jewett, Ivan ^a   Le Quement, Sebastian ^a   Marie, Jean Charles ^a   Muncipinto, Giovanni ^a   Duvall, Jeremy R ^a   Carmody, Leigh C ^a   Perez, Jose R ^a   Engel, Juan C ^b   Gut, Jiri ^b   Kellar, Danielle ^b   Siqueira Neto, Jair Lage ^b   McKerrow, James H ^b   Kaiser, Marcel ^c,d   Rodriguez, Ana ^e   Palmer, Michelle A ^a   Foley, Michael ^a   Schreiber, Stuart L ^a,f   Munoz, Benito ^a  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b University of California at San Francisco   (United States)

^c SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^d UNIVERSITY OF BASEL   (Switzerland)

^e NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f HARVARD UNIVERSITY   (United States)

Author keywords

Chagas disease; diversity oriented synthesis; high throughput screening; infectious disease; Molecular Libraries Probe Production Centers Network; neglected disease; phenotypic assay; Trypanosoma cruzi

Indexed keywords

ALCOHOL; AMINE; ANTIPARASITIC AGENT; BETA GALACTOSIDASE; ISONICOTINAMIDE; PHOSPHATE BUFFERED SALINE;

AMASTIGOTE; ARTICLE; CHAGAS DISEASE; CIS ISOMER; DRUG SYNTHESIS; FIBROBLAST; GROWTH INHIBITION; HIGH THROUGHPUT SCREENING; HOST CELL; HUMAN; IC 50; IN VITRO STUDY; LIFE CYCLE; MOLECULAR LIBRARY; MOUSE; MUSCLE CELL; MYOBLAST; NONHUMAN; ORGANIC CHEMISTRY; PLASMA PROTEIN BINDING; PRIORITY JOURNAL; SKELETAL MUSCLE; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; TRANS ISOMER; TRYPANOSOMA CRUZI; TRYPOMASTIGOTE;

EID: 84894050488     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml400403u     Document Type: Article

References (23)

1. Chagas disease 101. Nature 2010, 465, S4-S5.
2. Research priorities for Chagas disease, human African Trypanosomiasis and Leishmaniasis. World Health Organization's Technical Report Series 2012, 975, 1-116.
3. Bern, C.; Kjos, S.; Yabsley, M. J.; Montgomery, S. P. Trypanosoma cruzi and Chagas' disease in the United States Clin. Microbiol. Rev. 2011, 24, 655-681
4. Bern, C. Antitrypanosomal therapy for chronic Chagas' disease N. Engl. J. Med. 2011, 364, 2527-2534
5. Yun, O.; Lima, M. A.; Ellman, T.; Chambi, W.; Castillo, S.; Flevaud, L.; Roddy, P.; Parreno, F.; Vinas, P. A.; Palma, P. P. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Me'decins Sans Frontie'res PLoS Neglect. Trop. Dis. 2009, 3, e488
6. Chagas disease: pushing through the pipeline. Nature 2010, 465, S13-S15.
7. Villalta, F.; Dobish, M. C.; Nde, P. N.; Kleshchenko, Y. Y.; Hargrove, T. Y.; Johnson, C. A.; Waterman, M. R.; Johnston, J. N.; Lepesheva, G. I. VNI cures acute and chronic experimental Chagas disease J. Infect. Dis. 2013, 208, 504-511
8. Gunatilleke, S. S.; Calvet, C. M.; Johnston, J. B.; Chen, C. K.; Erenburg, G.; Gut, J.; Engel, J. C.; Ang, K. K.; Mulvaney, J.; Chen, S.; Arkin, M. R.; McKerrow, J. H.; Podust, L. M. Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51 PLoS. Negl. Trop. Dis. 2012, 6, e1736
9. Sajid, M.; Robertson, S. A.; Brinen, L. S.; McKerrow, J. H. Cruzain: the path from target validation to the clinic Adv. Exp. Med. Biol. 2011, 712, 100-115
10. Bahia, M. T.; de Andrade, I. M.; Martins, T. A.; do Nascimento, á. F.; Diniz Lde, F.; Caldas, I. S.; Talvani, A.; Trunz, B. B.; Torreele, E.; Ribeiro, I. Fexinidazole: a potential new drug candidate for Chagas disease PLoS Negl. Trop. Dis. 2012, 6, e1870
11. Butera, J. A. Phenotypic screening as a strategic component of drug discovery programs targeting novel antiparasitic and antimycobacterial agents: an editorial J. Med. Chem. 2013, 56, 7715-7718
12. Sykes, M. L.; Avery, V. M. Approaches to protozoan drug discovery: phenotypic screening J. Med. Chem. 2013, 56, 7727-7740
13. http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=624255 (accessed Dec 21, 2013).
14. O'Connell, K. M. G.; Galloway, W. R. J. D.; Spring, D. R. The basics of diversity-oriented synthesis. In Diversity Oriented Synthesis: Basics and Applications in Organic Synthesis, Drug Discovery and Chemical Biology; Trabocchi, A., Ed.; Wiley: New York, 2013; pp 1-26.
15. Dandapani, S.; Marcaurelle, L. A. Accessing new chemical space for 'undruggable' targets Nat. Chem. Biol. 2010, 6, 861-863
16. Schreiber, S. L. Organic synthesis toward small-molecule probes and drugs Proc. Natl. Acad. Sci. U.S.A. 2011, 26, 6699-6702
17. Marcaurelle, L. A.; Comer, E.; Dandapani, S.; Duvall, J. R.; Gerard, B.; Kesavan, S.; Lee, M. D.; Liu, H.; Lowe, J. T.; Marie, J. C.; Mulrooney, C. A.; Pandya, B. A.; Rowley, A.; Ryba, T. D.; Suh, B. C.; Wei, J.; Young, D. W.; Akella, L. B.; Ross, N. T.; Zhang, Y. L.; Fass, D. M.; Reis, S. A.; Zhao, W. N.; Haggarty, S. J.; Palmer, M.; Foley, M. A. An aldol-based build/couple/pair strategy for the synthesis of medium- and large-sized rings: Discovery of macrocyclic histone deacetylase inhibitors J. Am. Chem. Soc. 2010, 132, 16962-16976
18. Lowe, J. T.; Lee, M. D.; Akella, L. B.; Davoine, E.; Donckele, E. J.; Durak, L.; Duvall, J. R.; Gerard, B.; Holson, E. B.; Joliton, A.; Kesavan, S.; Lemercier, B. C.; Liu, H.; Marié, J. C.; Mulrooney, C. A.; Muncipinto, G.; Welzel-O'Shea, M.; Panko, L. M.; Rowley, A.; Suh, B. C.; Thomas, M.; Wagner, F. F.; Wei, J.; Foley, M. A.; Marcaurelle, L. A. Synthesis and profiling of a diverse collection of azetidine-based scaffolds for the development of CNS-focused lead-like libraries J. Org. Chem. 2012, 77, 7187-7211
19. NAr cycloetherification ACS Comb. Sci. 2011, 13, 365-374
20. Mulrooney, C. A.; Lahr, D. L.; Quintin, M. J.; Youngsaye, W.; Moccia, D.; Asiedu, J. K.; Mulligan, E. L.; Akella, L. B.; Marcaurelle, L. A.; Montgomery, P.; Bittker, J. A.; Clemons, P. A.; Brudz, S.; Dandapani, S.; Duvall, J. R.; Tolliday, N. J.; De Souza, A. J. Comput. Aided Mol. Des. 2013, 27, 455-468
21. Chou, D. H.; Duvall, J. R.; Gerard, B.; Liu, H.; Pandya, B. A.; Suh, B. C.; Forbeck, E. M.; Faloon, P.; Wagner, B. K.; Marcaurelle, L. A. Synthesis of a novel suppressor of beta-cell apoptosis via diversity-oriented synthesis ACS Med. Chem. Lett. 2011, 2, 698-702
22. Bettiol, E.; Samanovic, M.; Murkin, A. S.; Raper, J.; Buckner, F.; Rodriguez, A. Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening PLoS Negl. Trop. Dis. 2009, 3, e384
23. Doyle, P. S.; Zhou, Y. M.; Hsieh, I.; Greenbaum, D. C.; McKerrow, J. H.; Engel, J. C. The Trypanosoma cruzi protease cruzain mediates immune evasion PLoS Pathog. 2011, 7, e1002139