title: Synthesis and in vitro biological evaluation of dihydroartemisinyl-chalcone esters.
abstract: A series of dihydroartemisinyl-chalcone esters were synthesized through esterification of chalcones with dihydroartemisinin (DHA). The hybrids were screened against chloroquine (CQ) sensitive (3D7) and CQ resistant (W2) strains of intraerythrocytic Plasmodium falciparum parasites, and were all found to be active, with IC50 values ranging between 1.5 and 11 nM against both strains, with SI values over 5800. The esters featuring oxygenated aryl rings (7, 10 and 11), were found to be equipotent to DHA, but were 2-3 times more active than artesunate against the 3D7 and W2 strains of the malaria parasites. They were also screened in vitro against a panel of three cancer cell lines consisting of TK-10, UACC-62 and MCF-7. Compound 7, bearing a furan ring, displayed the most potent overall antitumor activity against all three cancer cell lines. TGA revealed that the targeted hybrids were all thermally more stable than DHA, which may be beneficial to the high temperature storage conditions that prevail in malaria endemic countries. During this study, ester 7 was identified as the best candidate for further investigation as a potential drug in search for new, safe and effective antimalarial drugs.
authors.affiliation: Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Smit
authors.affiliation: Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Riëtte A
authors.initials: RA
authors.lastname: van Biljon
authors.affiliation: Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria 0002, South Africa.
authors.forename: Lyn-Marie
authors.initials: LM
authors.lastname: Birkholtz
authors.affiliation: Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa. Electronic address: david.nda@nwu.ac.za.
authors.forename: David D
authors.initials: DD
authors.lastname: N'Da
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D004952:Esters; D002599:Chalcone; C039060:artenimol
keywords: Antitumor; Chalcone; Dihydroartemisinin; Malaria; Plasmodium falciparum