6533b856fe1ef96bd12b28ce

RESEARCH PRODUCT

Bistacrine derivatives as new potent antimalarials

Gabriele PradelInes SchmidtChe Julius NgwaAlexandra GolzmannLudmilla SologubTanja SchirmeisterAnna KucharskiUlrike Holzgrabe

subject

0301 basic medicinePlasmodiumSpectrometry Mass Electrospray IonizationStereochemistryProton Magnetic Resonance SpectroscopyClinical BiochemistryPharmaceutical Science01 natural sciencesBiochemistryAntimalarialsInhibitory Concentration 50Structure-Activity Relationship03 medical and health scienceschemistry.chemical_compoundChloroquineResistant strainDrug DiscoverymedicineAnimalsStructure–activity relationshipCarbon-13 Magnetic Resonance SpectroscopyCytotoxicityMolecular BiologyStrain (chemistry)010405 organic chemistryOrganic ChemistryCysteine protease0104 chemical sciences030104 developmental biologyMonomerchemistryBiochemistryTacrineTacrineMolecular MedicineDimerizationmedicine.drug

description

Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer. This finding prompted the synthesis of a library of monomeric and dimeric tacrine derivatives in order to derive structure-activity relationships. The most active compounds towards chloroquine sensitive Plasmodium strain 3D7 and chloroquine resistant strain Dd2 show IC50 values in the nanomolar range of concentration, low cytotoxicity and target the cysteine protease falcipain-2, which is essential for parasite growth.

yearjournalcountryeditionlanguage
2016-08-01Bioorganic & Medicinal Chemistry
https://doi.org/10.1016/j.bmc.2016.06.003