Leishmaniasis: current status of available drugs and new potential drug targets

Asian Pac J Trop Med. 2012 Jun;5(6):485-97. doi: 10.1016/S1995-7645(12)60084-4.

Abstract

The control of Leishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericin B, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aminoquinolines / therapeutic use
  • Amphotericin B / therapeutic use
  • Antigens, Protozoan / immunology
  • Antimony Sodium Gluconate / therapeutic use
  • Antiprotozoal Agents / therapeutic use*
  • Caspase Inhibitors
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Drug Discovery / trends
  • Enzyme Inhibitors / therapeutic use
  • Folic Acid Antagonists / therapeutic use
  • Humans
  • Leishmaniasis / drug therapy*
  • Leishmaniasis / enzymology
  • Macrophages / immunology
  • Microbodies / enzymology
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Paromomycin / therapeutic use
  • Pentamidine / therapeutic use
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / therapeutic use
  • Polyamines / antagonists & inhibitors
  • Polyamines / metabolism
  • Protease Inhibitors / therapeutic use
  • Sterols / biosynthesis
  • Sulfhydryl Compounds / metabolism
  • Topoisomerase Inhibitors / therapeutic use

Substances

  • Aminoquinolines
  • Antigens, Protozoan
  • Antiprotozoal Agents
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Folic Acid Antagonists
  • Polyamines
  • Protease Inhibitors
  • Sterols
  • Sulfhydryl Compounds
  • Topoisomerase Inhibitors
  • Phosphorylcholine
  • miltefosine
  • Paromomycin
  • Pentamidine
  • Amphotericin B
  • Cyclin-Dependent Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • 8-aminoquinoline
  • Antimony Sodium Gluconate