Trypanothione reductase (TR) is an enzyme found only in members of the Trypanosomatidae family. Several organisms belonging to this family are parasitic protozoa responsible for severe diseases including African trypanosomiasis (Trypanosoma brucei rhodesiense and T. b. gambiense), Chagas disease (T. cruzi) and leishmaniasis (Leishmania major, L. tropica and other species). Trypanothione reductase catalyzes the reduction of trypanothione (a glutathione-spermidine conjugate) by NADPH. Dihydrotrypanothione plays a vital role as a reducing agent in several metabolic processes in trypanosomatids. Several previous reports have shown that certain polyamine derivatives are inhibitors of TR, including spermine and spermidine derivatives with naphthylmethyl and 3-phenylpropyl substituents. We report the syntheses and inhibiting activities of novel analogs of these compounds that contain N-isopropyl substituents. These new compounds were designed as potential inhibitors of TR and to provide data for on-going structure activity relationship studies of polyamines as inhibitors of TR.

N-Isopropyl derivatives of aryl-substituted polyamines: Synthesis and inhibition of trypanothione reductase

255th National Meeting (2018)

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