Combinations of alkaloids affecting different molecular targets with the saponin digitonin can synergistically enhance trypanocidal activity against Trypanosoma brucei brucei

Antimicrobial Agents and Chemotherapy
Sonja KrstinMichael Wink

Abstract

The flagellate Trypanosoma brucei causes sleeping sickness in humans and nagana in animals. Only a few drugs are registered to treat trypanosomiasis, but those drugs show severe side effects. Also, because some pathogen strains have become resistant, new strategies are urgently needed to combat this parasitic disease. An underexplored possibility is the application of combinations of several trypanocidal agents, which may potentiate their trypanocidal activity in a synergistic fashion. In this study, the potential synergism of mutual combinations of bioactive alkaloids and alkaloids with a membrane-active steroidal saponin, digitonin, was explored with regard to their effect on T. b. brucei. Alkaloids were selected that affect different molecular targets: berberine and chelerythrine (intercalation of DNA), piperine (induction of apoptosis), vinblastine (inhibition of microtubule assembly), emetine (intercalation of DNA, inhibition of protein biosynthesis), homoharringtonine (inhibition of protein biosynthesis), and digitonin (membrane permeabilization and uptake facilitation of polar compounds). Most combinations resulted in an enhanced trypanocidal effect. The addition of digitonin significantly stimulated the activity of almo...Continue Reading

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Citations

Sep 14, 2016·International Journal of Molecular Sciences·Andrew CroakerLei Liu
Mar 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanmei LiMichael Wink
Jan 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fatahiya Mohamed TapNurul Bahiyah Ahmad Khairudin
May 22, 2018·Parasitology·Acidália Carine Vieira SantosMaria José Moreira Batatinha
Jul 2, 2020·Scientific Reports·Rafael C M Costa SilvaNorton Heise
Nov 24, 2020·Future Medicinal Chemistry·Nermin SamirMichael Wink

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