@article{fdi:010055802,
  title = {{B}iological activities of nitidine, a potential antimalarial lead compound},
  author = {{B}ouquet, {J}. and {R}ivaud, {M}. and {C}hevalley, {S}{\'e}verine and {D}eharo, {E}ric and {J}ullian, {V}al{\'e}rie and {V}alentin, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {N}itidine is thought to be the main active ingredient in several traditional anti-malarial remedies used in different parts of the world. {T}he widespread use of these therapies stresses the importance of studying this molecule in the context of malaria control. {H}owever, little is known about its potential as an anti-plasmodial drug, as well as its mechanism of action. {M}ethods: {I}n this study, the anti-malarial potential of nitidine was evaluated in vitro on {CQ}-sensitive and -resistant strains. {T}he nitidine's selectivity index compared with cancerous and non-cancerous cell lines was then determined. {I}n vivo assays were then performed, using the four-day {P}eter's test methodology. {T}o gain information about nitidine's possible mode of action, its moment of action on the parasite cell cycle was studied, and its localization inside the parasite was determined using confocal microscopy. {T}he in vitro abilities of nitidine to bind haem and to inhibit beta-haematin formation were also demonstrated. {R}esults: {N}itidine showed similar in vitro activity in {CQ}-sensitive and resistant strains, and also a satisfying selectivity index (> 10) when compared with a non-cancerous cells line. {I}ts in vivo activity was moderate; however, no sign of acute toxicity was observed during treatment. {N}itidine's moment of action on the parasite cycle showed that it could not interfere with {DNA} replication; this was consistent with the observation that nitidine did not localize in the nucleus, but rather in the cytoplasm of the parasite. {N}itidine was able to form a 1-1 complex with haem in vitro and also inhibited beta-haematin formation with the same potency as chloroquine. {C}onclusion: {N}itidine can be considered a potential anti-malarial lead compound. {I}ts ability to complex haem and inhibit beta-haematin formation suggests a mechanism of action similar to that of chloroquine. {T}he anti-malarial activity of nitidine could therefore be improved by structural modification of this molecule to increase its penetration of the digestive vacuole in the parasite, where haemoglobin metabolization takes place.},
  keywords = {},
  booktitle = {},
  journal = {{M}alaria {J}ournal},
  volume = {11},
  numero = {},
  pages = {67},
  ISSN = {1475-2875},
  year = {2012},
  DOI = {10.1186/1475-2875-11-67},
  URL = {https://www.documentation.ird.fr/hor/fdi:010055802},
}