Anticancer compounds as leishmanicidal drugs: challenges in chemotherapy and future perspectives.
Leishmaniasis comprises a spectrum of parasitic illnesses caused by several species of the protozoan kinetoplastid parasite, Leishmania spp. The disease affects 12 million people around the world with an annual death rate of approximately 80,000 people. Several drugs are available for treating leishmaniasis. For example, pentavalent antimonial compounds, such as sodium stibogluconate and meglumine antimonite are the drugs used in first-line chemotherapy. As second-line drugs, amphotericin B and pentamidine are used. However, current treatments against leishmaniasis are usually unsatisfactory due to some limitations including the route of administration of the drugs, their unaffordable cost and toxicity. Efforts have been made to develop new leishmanicidal drugs and to find new strategies of drug design. Hence, it is interesting to point out that the effectiveness of certain molecules as both anticancer drugs and antiprotozoal agents suggested that this class of compounds and their derivatives might be useful as antileishmanial agents. This review summarizes the anticancer compounds that have been investigated against leishmaniasis. Some of such agents include: compounds with in vitro antileishmanial activities, molecules tested in clinical trials and registered patents. We finally discuss challenges in chemotherapy and future prospects in the treatment of leishmaniasis.
Fuertes
Miguel A
MA
Centro de Biología Molecular Severo Ochua, CSIC-UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Nguewa
Paul A
PA
Castilla
Josefina
J
Alonso
Carlos
C
Pérez
José M
JM
D000677:Amsacrine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D008536:Meglumine / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000627:therapeutic use; D010743:Phospholipids / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D010743:Phospholipids; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; C022202:9-anilinoacridine; D015125:Oxyquinoline; D008536:Meglumine; D000077485:Meglumine Antimoniate