Donnerstag, 5. Dezember 2013

Previewed Publications - Artemisinin Anticancer Properties

Sehr geehrter Herr Papendorf,

das ist in der Tat eine sehr interessante Substanz, ich habe noch etwas darüber gelesen und schicke Ihnen in der Anlage noch 2 Arbeiten.

Alles Gute und einen schönen 2. Advent.


Peter Hammerer

Prof. Dr. Peter Hammerer
Chefarzt Klinik für Urologie und Uroonkologie
Klinikum Braunschweig
Salzdahlumer Str. 90
D 38126 Braunschweig
Tel.: +49 531 595 2312
Fax: +49 531 595 2657

Anticancer Properties of Distinct Antimalarial Drug Classes

Anticancer Properties of Distinct Antimalarial Drug Classes

  • Rob Hooft van Huijsduijnen, R. Kiplin Guy, Kelly Chibale, Richard K. Haynes, Ingmar Peitz, Gerhard Kelter, Margaret A. Phillips, Jonathan L. Vennerstrom, Yongyuth Yuthavong, Timothy N. C. Wells mail

  • Published: December 31, 2013
  • DOI: 10.1371/journal.pone.0082962


We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents

Molecules 2014, 19(11), 19021-19035; doi:10.3390/molecules191119021

Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents

1,†, 2, 1, 3, 1, 1, 1, 3, 2,*  and 1,*

Abstract: A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (79, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.
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