In vitro activity of the beta-carboline alkaloids harmane, harmine, and harmaline toward parasites of the species Leishmania infantum.
Harmane, harmine, and harmaline were investigated for their in vitro antileishmanial activity toward parasites of the species Leishmania infantum. Harmane and Harmine displayed a moderate antiproliferative activity toward human monocytes and exerted a weak antileishmanial activity toward both the promastigote and the amastigote forms of the parasite. Their mechanism of action on the promastigote form of the parasite involved interactions with DNA metabolism leading to an accumulation of parasites in the S-G(2)M phases of the cell-cycle. Harmaline, at the contrary, was deprived from toxicity toward human cells and Leishmania promastigotes, however it exerted a strong antileishmanial activity toward the intracellular amastigote form of the parasite. This property was shown to partly result from the capacity of the molecule to prevent parasite internalization within macrophages by inhibiting Leishmania PKC activity.
Di Giorgio
C
C
Laboratoire de Parasitologie, Hygiène et Zoologie Facultè de Pharmacie, 27 Bd. Jean Moulin, 13385 Marseille cedex 05, France. Carole.Digiorgio@pharmaciie.univ-mrs.fr
Delmas
F
F
Ollivier
E
E
Elias
R
R
Balansard
G
G
Timon-David
P
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D006246:Harmaline / Q000737:chemistry / Q000494:pharmacology*; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008564:Membrane Potentials / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects
D000981:Antiprotozoal Agents; D006247:Harmine; C005010:harman; D006246:Harmaline; D011493:Protein Kinase C