Smit F.J., Van Biljon R.A., Birkholtz L.-M., N'da D.D.
Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa; Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa
Smit, F.J., Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa; Van Biljon, R.A., Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa; Birkholtz, L.-M., Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa; N'da, D.D., Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
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 IC<inf>50</inf> 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. © 2014 Elsevier Masson SAS.
10 aplha dihydroartemisinyl 4 [(1e) 3 (5 methylfuran 2 yl) 3 oxoprop 1 en 1 yl]benzoate; 10 beta dihydroartemisinyl 4 [[(1e) 3 oxo 3 (2,3,4 trichlorophenyl)]prop 1 en yl]benzoate; 10 dihydroartemisinyl 4 [(1e) 3 oxo 3 phenylprop 1 en 1 yl]benzoate; 10 dihydroartemisinyl 4 [[(1e) 3 (2,4 dimethoxyphenyl)] 3 oxoprop 1 en 1 yl]benzoate; 10 dihydroartemisinyl 4 [[(1e) 3 (3 methoxy 4 nitrophenyl)] 3 oxoprop 1 en 1 yl]benzoate; 10 dihydroartemisinyl 4 [[(1e) 3 (3,4 dimethoxyphenyl)] 3 oxoprop 1 en 1 yl]benzoate; 4 [(1e) 3 oxo 3 phenylprop 1 en 1 yl]benzoic acid; 4 [[(1e) 3 (2,4 dimethoxyphenyl)] 3 oxoprop 1 en 1 yl]benzoic acid; 4 [[(1e) 3 (3 methoxy 4 nitrophenyl)] 3 oxoprop 1 en 1 yl]benzoic acid; 4 [[(1e) 3 (3,4 dimethoxyphenyl)] 3 oxoprop 1 en 1 yl]benzoic acid; 4 [[(1e) 3 (5 methylfuran 2 yl)] 3 oxoprop 1 en 1 yl]benzoic acid; 4 [[(1e) 3 oxo 3 (2,3,4 trichlorophenyl)]prop 1 en 1 yl]benzoic acid; antimalarial agent; antineoplastic agent; artesunate; chalcone derivative; chloroquine; dihydroartemisinin; dihydroartemisinin derivative; dihydroartemisinyl chalcone ester; ester derivative; furan; unclassified drug; antimalarial agent; antineoplastic agent; artemisinin derivative; chalcone; ester; antimalarial activity; antineoplastic activity; Article; cancer cell line; controlled study; drug screening; drug stability; drug storage; drug synthesis; high temperature; human; human cell; IC50; in vitro study; nonhuman; Plasmodium falciparum; storage temperature; structure activity relation; cell proliferation; chemical structure; chemistry; dose response; drug effects; drug sensitivity; MCF 7 cell line; synthesis; tumor cell line; Antimalarials; Antineoplastic Agents; Artemisinins; Cell Line, Tumor; Cell Proliferation; Chalcone; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esters; Humans; MCF-7 Cells; Molecular Structure; Parasitic Sensitivity Tests; Plasmodium falciparum; Structure-Activity Relationship