Abstract
There is an urgent need to develop a safe, effective, orally active, and inexpensive therapy for African trypanosomiasis due to the drawbacks of current drugs. Selective tubulin inhibitors have the potential to be promising drug candidates for the treatment of this disease, which is based on the tubulin protein structural difference between mammalian and trypanosome cells. We propose to identify novel tubulin inhibitors from a compound library developed based on the lead compounds that selectively target trypanosomiasis. We used Trypanosoma brucei brucei as the parasite model, and human normal kidney cells and mouse microphage cells as the host model. Growth rates of both trypanosomes and mammalian cells were determined as a means to screen compounds that selectively inhibit the proliferation of parasites. Furthermore, we examined the cell cycle profile of the parasite and compared tubulin polymerization dynamics before and after the treatment using identified compounds. Last, in vivo anti-parasite activities of these compounds were determined in T. brucei-infected mice. Three compounds were selected that are 100 fold more effective against the growth of T. brucei cells than mammalian cells. These compounds caused cell cycle pr...Continue Reading
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Citations
Aug 16, 2018·MedChemComm·Michael BerningerUlrike Holzgrabe
Mar 6, 2019·Bioorganic & Medicinal Chemistry·Anran ZhaoBin Su
May 13, 2021·Biomedical Chromatography : BMC·Yaxin LiBin Su
Jun 8, 2019·Veterinary Parasitology: X·Roger Ramirez-BarriosPhilippe Holzmuller
Sep 18, 2018·ACS Omega·Dinabandhu SarDipanjan Pan