Novel approaches for the identification of inhibitors of leishmanial dipeptidylcarboxypeptidase.

INTRODUCTION

Leishmaniasis imposes a substantial burden of mortality and morbidity affecting 12 million globally and continues to be a neglected tropical disease. Control of the disease is mainly based on chemotherapy, which relies on a handful of drugs with serious limitations. Over the last decade, target-based drug discovery is also being employed in addition to the random screening of compounds. Leishmanial dipeptidylcarboxypeptidase (LDCP), an angiotensin converting enzyme (ACE) related metallopeptidase, has been recently identified as a novel drug target for antileishmanial chemotherapy.

AREAS COVERED

This article examines dipeptidylcarboxypeptidase (DCP) of Leishmania donovani and of other sources from the international literature regarding their biochemical and structural characterization in comparison to mammalian ACE. Furthermore, the author discusses the identification of LdDCP specific inhibitors by virtual screening and their effect on parasite multiplication. Finally, the review looks ahead at areas for further exploration of DCP inhibitors in Leishmania chemotherapy.

EXPERT OPINION

The first step in targeted screening is to identify a suitable drug target and its validation followed by its use in high throughput screening of compounds. Limited studies on LDCP inhibitors have established a good correlation between parasite enzyme inhibition and their biological activity. This suggests that there is a potential for LDCP inhibitors as new antileishmanial drugs.