title: Inhibition of rhodesain as a novel therapeutic modality for human African trypanosomiasis.
abstract: Rhodesain, a cathepsin L-like cysteine protease of T. brucei rhodesiense, is considered a potential target for the treatment of human African trypanosomiasis. Recent findings have confirmed that rhodesain, a lysosomal protease, is essential for parasite survival. Rhodesain is required by T. brucei to cross the blood-brain barrier, degrade host immunoglobulins, and turn over variant surface coat glycoproteins of T. brucei, which impair effective host immune responses. In this Perspective, we discuss the main classes of rhodesain inhibitors, including peptidic, peptidomimetic, and nonpeptidic structures, emphasizing those that have exhibited an optimal match between enzymatic affinity and trypanocidal profile and those for which preclinical investigations are currently in progress.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano , Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.forename: Lucia
authors.initials: L
authors.lastname: Tamborini
authors.forename: Ilenia C
authors.initials: IC
authors.lastname: Angelo
authors.forename: Nicola
authors.initials: N
authors.lastname: Micale
authors.forename: Andrea
authors.initials: A
authors.lastname: Pinto
authors.forename: Carlo
authors.initials: C
authors.lastname: De Micheli
authors.forename: Paola
authors.initials: P
authors.lastname: Conti
mesh_terms: D056668:Cathepsin L / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi; C446033:rhodesain; D056668:Cathepsin L