Promising therapeutic targets for antileishmanial drugs.
Current treatments for the parasitic disease leishmaniasis are unsatisfactory due to their route of administration, toxicity and expense. Resistance is also developing to first-line antimonial drugs. Fortunately, a handful of antileishmanial agents, such as the orally available compound miltefosine, are currently in clinical trials. In addition, several promising drug targets and lead molecules are being studied with the goal of developing new antileishmanial agents. Drug candidates have been identified through the continued investigation of parasite sterol metabolism and parasite proteases. New antileishmanial molecules have also been discovered through the study of novel targets and pathways, such as the bisphosphonate inhibitors of isoprenoid biosynthesis. This review presents a synopsis of the drug targets and lead compounds that have been investigated over the last few years against leishmaniasis, gives a perspective on the chemotherapeutic potential of each and discusses some of the obstacles to antileishmanial drug development.
Werbovetz
Karl A
KA
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA. werbovetz.1@osu.edu
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047188:Chalcones / Q000378:metabolism; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005493:Folic Acid Antagonists / Q000378:metabolism; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D050356:Lipid Metabolism / Q000187:drug effects; D010419:Pentamidine / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D014404:Tubulin / Q000187:drug effects
D000981:Antiprotozoal Agents; D047188:Chalcones; D005493:Folic Acid Antagonists; D011073:Polyamines; D015800:Protozoan Proteins; D014404:Tubulin; D010419:Pentamidine