Expanding the biological application of fluorescent benzothiadiazole derivatives: a phenotypic screening strategy for anthelmintic drug discovery using caenorhabditis elegans
SLAS Discov
; 24(7): p. 755-765, 2019.
Article
in English
| Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP
| ID: but-ib16081
Responsible library:
BR78.1
Localization: BR78.1
ABSTRACT
The current methodologies used to identify promising new anthelmintic compounds rely on subjective microscopic examination of worm motility or involve genetic modified organisms. We describe a new methodology to detect worm viability that takes advantage of the differential incorporation of the fluorescent molecular marker propidium iodide and the 2,1,3-benzothiadiazole core, which has been widely applied in light technology. The new assay developed could be validated using the "Pathogen Box" library. By use of this bioassay, it was possible to identify three molecules with activity against Caenorhabditis elegans that were previously described as effective in in vitro assays against other pathogens, such as Schistosoma mansoni, Mycobacterium tuberculosis, and Plasmodium falciparum, accelerating the identification of molecules with anthelmintic potential. The current fluorescence-based bioassay may be used for assessing C. elegans viability. The described methodology replaces the subjectivity of previous assays and provides an enabling technology that is useful for rapid in vitro screens of both natural and synthetic compound libraries. It is expected that the results obtained from these robust in vitro screens would select the most effective compounds for follow-up in vivo experimentation with pathogenic helminths.
Full text:
Available
Collection:
National databases
/
Brazil
Database:
Sec. Est. Saúde SP
/
SESSP-IBPROD
Language:
English
Journal:
SLAS Discov
Year:
2019
Document type:
Article