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Molecules 2017, 22(11), 1954;

Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain

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
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, R. Weigla Street, 53-114 Wroclaw, Poland
Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
Department of Chemistry and Materials Engineering, Yingkou Institute of Technology, Yingkou 115014, China
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom 32511, Egypt
Authors to whom correspondence should be addressed.
Received: 14 October 2017 / Revised: 3 November 2017 / Accepted: 10 November 2017 / Published: 12 November 2017
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Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted 5-methyl-indolo[2,3-b]quinoline derivatives were prepared by nucleophilic aromatic substitution (SNAr) of 11-chloroneocryptolepines with appropriate 1,2- and 1,3-diamines. Some of the 11-(ω-aminoalkylamino) derivatives were further transformed into 11-ureido and thioureido analogues. Many of the prepared neocryptolepine derivatives showed submicromolar antiproliferative activity against the human leukemia MV4-11 cell line. Among them, 11-(3-amino-2-hydroxy)propylamino derivatives 2h and 2k were the most cytotoxic with a mean IC50 value of 0.042 μM and 0.057 μM against the MV4-11 cell line, 0.197 μM and 0.1988 μM against the A549 cell line, and 0.138 μM and 0.117 μM against the BALB/3T3 cell line, respectively. View Full-Text
Keywords: indolo[2,3-b]quinolone; neocryptolepine; antiproliferative activity; SAR study; aminoalkylamino-substituted indolo[2,3-b]quinolone; neocryptolepine; antiproliferative activity; SAR study; aminoalkylamino-substituted

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Shaban, E.; Świtalska, M.; Wang, L.; Wang, N.; Xiu, F.; Hayashi, I.; Ngoc, T.A.; Nagae, S.; El-Ghlban, S.; Shimoda, S.; Gokha, A.A.A.E.; Sayed, I.E.T.E.; Wietrzyk, J.; Inokuchi, T. Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain. Molecules 2017, 22, 1954.

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