Drug combination studies of PS-1 and quercetin against rhodesain of Trypanosoma brucei rhodesiense

Abstract

Rhodesain is a cysteine protease crucial for the survival of Trypanosoma brucei rhodesiense, the parasite able to induce the acute lethal form of Human African Trypanosomiasis. PS-1 is a synthetic peptidyl inhibitor of rhodesain, characterised by a picomolar binding affinity (K_i = 1.1 pM). Thus, considering the well-known antiparasitic properties of quercetin, in this study, we decided to carry out drug combination studies of PS-1 and quercetin against rhodesain, according to Chou and Talalay method, which allowed us to obtain for the most relevant f_a values a nearly additive effect for the reduction of rhodesain activity from 40% to 90%, thus considering a promising strategy their use in combination.

Graphical Abstract

Keywords:

• rhodesain
• drug combination studies
• quercetin
• synthetic inhibitor
• additive effect

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the ‘FFABR 2020’ financed by UNIME.