Skip to content

Research at St Andrews

Screening of the MMV and GSK open access chemical boxes using a viability assay developed against the kinetoplastid Crithidia fasciculata

Research output: Contribution to journalArticle

Abstract

Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes. The screening assay had an average Z’ factor of 0.7 and tolerated a maximum dimethyl sulfoxide concentration of up to 0.5%. We identified from multiple chemical boxes two compound series exhibiting nanomolar potency against C. fasciculata, one centred around a 5-nitrofuran-2-yl scaffold, a well-known moiety in several existing anti-infectives, and another involving a 2-(pyridin-2-yl) pyrimidin-4-amine scaffold which seems to have pan-kinetoplastid activity. This work facilitates the future use of C. fasciculata as a non-pathogenic and inexpensive biological resource to identify mode of action/protein target(s) of potentially pan-trypanocidal potent compounds. This knowledge will aid in the development of new treatments for African sleeping sickness, Chagas disease and leishmaniasis.
Close

Details

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume222
Early online date18 May 2018
DOIs
Publication statusPublished - Jun 2018

    Research areas

  • Crithidia fasciculata, Kinetoplastid, Drug discovery

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Substrate specificity of the neutral sphingomyelinase from Trypanosoma brucei

    Dickie, E. A., Young, S. A. & Smith, T. K., Apr 2019, In : Parasitology. 146, 5, p. 604-616 13 p.

    Research output: Contribution to journalArticle

  2. Branched late-steps of the cytosolic iron-sulphur cluster assembly machinery of Trypanosoma brucei

    Tonini, M. L., Peña-Diaz, P., Haindrich, A. C., Basu, S., Kriegová, E., Pierik, A. J., Lill, R., MacNeill, S. A., Smith, T. K. & Lukeš, J., 22 Oct 2018, In : PLoS Pathogens. 14, 10, 31 p., e1007326.

    Research output: Contribution to journalArticle

  3. Structure-based design of a eukaryote-selective antiprotozoal fluorinated aminoglycoside

    Kanazawa, H., Saavedra, O. M., Maianti, J. P., Young, S. A., Izquierdo, L., Smith, T. K., Hanessian, S. & Kondo, J., 10 Aug 2018, In : ChemMedChem. 13, 15, p. 1541-1548 8 p.

    Research output: Contribution to journalArticle

  4. ADIPOSE TISSUE IS A MAJOR RESERVOIR OF FUNCTIONALLY DISTINCT TRYPANOSOMA BRUCEI PARASITES

    Trindade, S., Rijo-Ferreira, F., Carvalho, T., Pinto-Neves, D., Guegan, F., Aresta-Branco, F., Bento, F., Young, S. A., Pinto, A., Van den Abbeele, J., Ribeiro, R. M., Dias, S., Smith, T. K. & Figueiredo, L. M., Nov 2017, In : American Journal of Tropical Medicine and Hygiene. 95, 5, p. 606-606 1 p.

    Research output: Contribution to journalAbstract

Related by journal

  1. Molecular and Biochemical Parasitology (Journal)

    Terry K Smith (Member of editorial board)
    2015 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms

    Surve, S. V., Jensen, B. C., Heestand, M., Mazet, M., Smith, T. K., Bringaud, F., Parsons, M. & Schnaufer, A., Jan 2017, In : Molecular and Biochemical Parasitology. 211, p. 57-61 5 p.

    Research output: Contribution to journalArticle

  2. Lipid metabolism in Trypanosoma brucei

    Smith, T. K. & Buetikofer, P., Aug 2010, In : Molecular and Biochemical Parasitology. 172, 2, p. 66-79 14 p.

    Research output: Contribution to journalReview article

  3. Expressed sequence tag (EST) analysis of the pine wood nematode Bursaphelenchus xylophilus and B-mucronatus

    Kikuchi, T., Aikawa, T., Kosaka, H., Pritchard, L., Ogura, N. & Jones, J. T., Sep 2007, In : Molecular and Biochemical Parasitology. 155, 1, p. 9-17 9 p.

    Research output: Contribution to journalArticle

ID: 253137217