Synthesis and Effects on Chloroquine Susceptibility in Plasmodium falciparum of a Series of New Dihydroanthracene Derivatives

Abstract
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.