Molecular insights into trypanothione reductase-inhibitor interaction: A structure-based review.

Information on how small molecules bind to the target enzyme has the potential to impact immensely on how medicinal chemists go about antiparasitic drug discovery. In this review, for the first time, we intend to make an assessment of the structural aspects of trypanothione reductase as drug target, and its complexes with several reversible drugs from the Protein Data Bank (PDB). We attempt to reveal the mechanism of these interactions by careful accounting of the X-ray structures and their possible roles in biological activity to treat Trypanosomatidae diseases. We focus on some of the outstanding findings from structures that are relevant to anti-trypanocidal drug discovery. We also review new interesting compounds that have appeared in the literature based on these X-ray structures.