Phenothiazine Inhibitors of Trypanothione Reductase as Potential Antitrypanosomal and Antileishmanial Drugs

A Critical Review on Chagas Disease Chemotherapy

“…A first group of inhibitors reported were the so-called "subversive substrates", due to the futile-cycling of TR induced by redox-damaging drugs, such as nitrofurans, and naphtoquinones (Henderson et al 1988, Salmon-Chemin et al 2001. Subsequently the structure of tricyclic neuroleptic showed to be a promising backbone class of TR inhibitors, and based on computational design techniques several tricylcic compounds were investigated (Chan et al 1998, Gutierrez-Correa et al 2001. Some compounds of the series of 2-amino diphenylsulfides, that have lower neuroleptic activity than phenothiazines, were potent inhibitors of TR (Girault et al 1998).…”

Synthesis and antileishmanial activity of novel pyridinium-hydrazone derivatives

“…However, the exact mode of action has not been elucidated yet, it can be speculated that the cationic pyridinium moiety of the compounds may have an interaction potency with DNA and/or other biological nucleophilles 40,41 . These final compounds are capable of making ionic and hidrogen bonds as well as ion-dipol, dipol-dipol, hydrophobic interactions with biological components 40 .…”

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

“…The selection of study drugs has been eclectic and largely empiric, and their broad array defies useful classification. However, rational or structure-based drug design has also begun to be applied (40,155), with appropriate concern for validating putative therapeutic targets (19). Results for a number of the new antileishmanial compounds have been reported in just the past several years, making it difficult to judge their potential usefulness.…”