Synthesis and effects on chloroquine susceptibility in Plasmodium falciparum of a series of new dihydroanthracene derivatives.
To suggest a mechanism of action for drugs capable to reverse the chloroquine resistance, a new set of 9,10-dihydro-9,10-ethano and ethenoanthracene derivatives was synthesized and compounds were tested with the aim to assess their effect on chloroquine susceptibility in Plasmodium falciparum resistant strains. With respect to this, reversal of resistance and change in drug accumulation were compared. Structure-activity relationship and molecular modeling studies made it possible to define a pharmacophoric moiety for reversal agents and to propose a putative model of interaction with some selected amino acids.
GERCTOP-UMR CNRS 6009, Faculté de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille, France.
Sandrine
S
Alibert
Christiane
C
Santelli-Rouvier
Bruno
B
Pradines
Carole
C
Houdoin
Daniel
D
Parzy
Janina
J
Karolak-Wojciechowska
Jacques
J
Barbe
D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D018432:Drug Resistance, Multiple; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D066298:In Vitro Techniques; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000873:Anthracenes; D000962:Antimalarials; D002738:Chloroquine