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Trypanocidal curcumin analog forms an adduct with trypanothione
An international effort led by the University of Glasgow has brought forth the development of potent trypanocidal curcumin analogs bearing a monoenone linker motif that acts on Trypanosoma brucei (T. brucei) by forming an adduct with trypanothione. The objective of this study is to evaluate the use of these curcumin analogs as antiparasitic agents by comparing the cellular effects of curcumin and the enone linker lead compound AS-HK014, which was previously developed as a drug to eliminate trypanosomes before they developed AS-HK014 resistance. Elucidating the mechanism by which curcuminoids affect trypanosomes should lead to a more solid understanding of their trypanocidal potential and help reveal other anti-infective applications of curcuminoids.
As part of the comprehensive analysis of biological effects of curcumin analogs and AS-HK014 on T. brucei, plasma membrane conductance and signaling was scrutinized by observing changes in wild type parasite plasma membrane potential, calcium conductance, and cAMP intracellular levels, upon application of curcumin and monoenone analogs. Respectively, the parameters were measured through use of fluorescent probes bisoxonol and Fluo-8® from the Screen Quest™ Fluo-8 Calcium Kit, and a cAMP immunoassay kit. The results of this analysis showed that none of the curcumin and monoenone analogs had a significant effect on any of the parameters regarding plasma membrane function, indicating that the drugs' trypanocidal effects were not due to disruption of plasma membrane integrity.
This investigation of T. brucei membrane biology progressed in a timely manner thanks to the accuracy and convenience of both fluorescent probes and simplified kits. The Screen Quest™ Fluo-8 Calcium Kit combines the best advantages of both approaches, by providing all necessary reagents for use of proprietary calcium dye Fluo-8®. Fluo-8®'s brilliant and sensitive fluorescent signal, convenient spectrum, and enhanced properties toward easier cell loading make it a valuable addition to your tools for parasitological study.
As part of the comprehensive analysis of biological effects of curcumin analogs and AS-HK014 on T. brucei, plasma membrane conductance and signaling was scrutinized by observing changes in wild type parasite plasma membrane potential, calcium conductance, and cAMP intracellular levels, upon application of curcumin and monoenone analogs. Respectively, the parameters were measured through use of fluorescent probes bisoxonol and Fluo-8® from the Screen Quest™ Fluo-8 Calcium Kit, and a cAMP immunoassay kit. The results of this analysis showed that none of the curcumin and monoenone analogs had a significant effect on any of the parameters regarding plasma membrane function, indicating that the drugs' trypanocidal effects were not due to disruption of plasma membrane integrity.
This investigation of T. brucei membrane biology progressed in a timely manner thanks to the accuracy and convenience of both fluorescent probes and simplified kits. The Screen Quest™ Fluo-8 Calcium Kit combines the best advantages of both approaches, by providing all necessary reagents for use of proprietary calcium dye Fluo-8®. Fluo-8®'s brilliant and sensitive fluorescent signal, convenient spectrum, and enhanced properties toward easier cell loading make it a valuable addition to your tools for parasitological study.
References
- Alkhaldi AA, Creek DJ, Ibrahim H1, Kim DH, Quashie NB, Burgess KE, Changtam C, Barrett MP, Suksamrarn A, de Koning HP. Potent trypanocidal curcumin analogs bearing a monoenone linker motif act on trypanosoma brucei by forming an adduct with trypanothione. Mol Pharmacol. 2015;87(3):451-64. doi: 10.1124/mol.114.096016. Epub 2014 Dec 19.
- Screen Quest™ Fluo-8 Medium Removal Calcium Assay Kit. AAT Bioquest, n.d. Web. 13 July 2016
Original created on January 12, 2017, last updated on January 12, 2017
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