title: Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents.
abstract: A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a-7f, 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 (7-9, 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.
authors.affiliation: 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. liwang_512@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Science, 12, R. Weigl Street, Wroclaw 53-114, Poland. switalska@iitd.pan.wroc.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Świtalska
authors.affiliation: 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. wn12171982@sina.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Okayama University of Science, Ridai-cho, Kita-ku, Okayama, Japan. duzhenjun@hotmail.com.
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Du
authors.affiliation: 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. en422758@s.okayama-u.ac.jp.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Fukumoto
authors.affiliation: 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. Nguyen-Kim.Diep@unilever.com.
authors.forename: Nguyen Kim
authors.initials: NK
authors.lastname: Diep
authors.affiliation: 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. a-k_g.dempsey.20_49@docomo.ne.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kiguchi
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Okayama University of Science, Ridai-cho, Kita-ku, Okayama, Japan. nogami@dac.ous.ac.jp.
authors.forename: Junzo
authors.initials: J
authors.lastname: Nokami
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Science, 12, R. Weigl Street, Wroclaw 53-114, Poland. wietrzyk@iitd.pan.wroc.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: 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. inokuchi@cc.okayama-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Inokuchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D037621:Artemisinins / Q000138:chemical synthesis* / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D011804:Quinolines; C039060:artenimol; C031327:artemisinin; C037219:quinoline