@article{PAR00008074,
  title = {{I}ndolone-{N}-oxide derivatives : in vitro activity against fresh clinical isolates of {P}lasmodium falciparum, stage specificity and in vitro interactions with established antimalarial drugs},
  author = {{T}ahar, {R}achida and {V}ivas, {L}. and {B}asco, {L}eonardo and {T}hompson, {E}. and {I}brahim, {H}. and {B}oyer, {J}. and {N}epveu, {F}.},
  editor = {},
  language = {{ENG}},
  abstract = {{O}bjectives: {I}ndolone-{N}-oxides are characterized by the presence of a highly reactive pharmacophore, the nitrone moiety ({C}={N}+-{O}-), which undergoes oxidation-reduction reactions. {T}he aims of the present study were to: (i) evaluate the in vitro activity of the parent compound, designated as compound 1, against 34 fresh clinical isolates of {P}lasmodium falciparum; (ii) compare the activity of compound 1 with that of chloroquine and dihydroartemisinin to assess the potential for cross-resistance; (iii) investigate drug interactions of indolone-{N}-oxides with standard antimalarials; and (iv) determine the stage-dependent activity of indolone-{N}-oxides. {M}ethods: {I}n vitro antimalarial activity was evaluated against clinical isolates collected from {C}ameroonian patients by the [{H}-3]hypoxanthine incorporation assay. {I}n vitro interactions between compound 1 or another analogue, compound 4, and established antimalarial drugs were assessed by the fixed ratio method. {S}tage specificity was evaluated by light microscopy using highly synchronized {P}. falciparum cultures. {R}esults: {T}he geometric mean 50% inhibitory concentration ({IC}50) of compound 1 was 48.6 n{M}. {I}ts activity did not differ between the chloroquine-susceptible and the chloroquine-resistant isolates. {T}here was no correlation between chloroquine and compound 1 responses (r=0.015; {P}>0.05), but the in vitro responses of compound 1 and dihydroartemisinin were significantly and positively correlated (r=0.444; {P}<0.05). {N}o significant in vitro interaction was observed between indolone-{N}-oxide derivatives and established antimalarial drugs (artemisinin and its derivatives, chloroquine, amodiaquine, quinine and mefloquine). {C}ompound 1 and compound 4, as well as artesunate, inhibited parasite maturation at the ring stage. {C}onclusions: {T}hese findings suggest that other indolone-{N}-oxide derivatives with more potent activity than the parent compound may hold promise as antimalarials in the future.},
  keywords = {antimalarial drugs ; drug resistance ; chloroquine ; artemisinin ; redox},
  booktitle = {},
  journal = {{J}ournal of {A}ntimicrobial {C}hemotherapy},
  volume = {66},
  numero = {11},
  pages = {2566--2572},
  ISSN = {0305-7453},
  year = {2011},
  DOI = {10.1093/jac/dkr320},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00008074},
}