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Molecules 2017, 22(11), 1954; doi:10.3390/molecules22111954

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

1
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
2
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, R. Weigla Street, 53-114 Wroclaw, Poland
3
Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
4
Department of Chemistry and Materials Engineering, Yingkou Institute of Technology, Yingkou 115014, China
5
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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Abstract

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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