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Molecules 2014, 19(11), 19021-19035;

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

Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan
Institute of Immunology and Experimental Therapy, Polish Academy of Science, 12, R. Weigl Street, Wroclaw 53-114, Poland
Department of Applied Chemistry, Faculty of Engineering, Okayama University of Science, Ridai-cho, Kita-ku, Okayama, Japan
Present Addresses: Pharmacy Department, Luzhou Medical College, Lu zhou 646000, China.
Authors to whom correspondence should be addressed.
Received: 13 August 2014 / Revised: 10 November 2014 / Accepted: 12 November 2014 / Published: 18 November 2014
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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. View Full-Text
Keywords: artemisinin; indoloquinoline; hybrid; antiproliferative activity; cytotoxicity artemisinin; indoloquinoline; hybrid; antiproliferative activity; cytotoxicity

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wang, L.; Świtalska, M.; Wang, N.; Du, Z.-J.; Fukumoto, Y.; Diep, N.K.; Kiguchi, R.; Nokami, J.; Wietrzyk, J.; Inokuchi, T. Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents. Molecules 2014, 19, 19021-19035.

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