biostudies-literaturePreviti SUniversity of Messina3765https://www.ebi.ac.uk/biostudies/studies/S-EPMC9229991biostudies-literatureUnknown27(12)Human African Trypanosomiasis (HAT) is an endemic protozoan disease widespread in the sub-Saharan region that is caused by <i>T. b. gambiense</i> and <i>T. b. rhodesiense</i>. The development of molecules targeting rhodesain, the main cysteine protease of <i>T. b. rhodesiense</i>, has led to a panel of inhibitors endowed with micro/sub-micromolar activity towards the protozoa. However, whilst impressive binding affinity against rhodesain has been observed, the limited selectivity towards the target still remains a hard challenge for the development of antitrypanosomal agents. In this paper, we report the synthesis, biological evaluation, as well as docking studies of a series of reduced peptide bond pseudopeptide Michael acceptors (<b>SPR10</b>-<b>SPR19</b>) as potential anti-HAT agents. TMolecules (Basel, Switzerland)Development of Reduced Peptide Bond Pseudopeptide Michael Acceptors for the Treatment of Human African Trypanosomiasis.PMC9229991FFABR 2020Bogacz MCosconati SDi Chio CEttari RPreviti SRavichandran RSchirmeister THellmich UAZappala MfalseDevelopment of Reduced Peptide Bond Pseudopeptide Michael Acceptors for the Treatment of Human African Trypanosomiasis.Human African Trypanosomiasis (HAT) is an endemic protozoan disease widespread in the sub-Saharan region that is caused by <i>T. b. gambiense</i> and <i>T. b. rhodesiense</i>. The development of molecules targeting rhodesain, the main cysteine protease of <i>T. b. rhodesiense</i>, has led to a panel of inhibitors endowed with micro/sub-micromolar activity towards the protozoa. However, whilst impressive binding affinity against rhodesain has been observed, the limited selectivity towards the target still remains a hard challenge for the development of antitrypanosomal agents. In this paper, we report the synthesis, biological evaluation, as well as docking studies of a series of reduced peptide bond pseudopeptide Michael acceptors (<b>SPR10</b>-<b>SPR19</b>) as potential anti-HAT agents. T2022-01-01T00:00:00Z2022 Jun2025-05-29T19:47:07.642Z2025-04-05T07:15:36.912ZS-EPMC92299913574489110.3390/molecules27123765