Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain
Elkhabiry Shaban,
Marta Świtalska,
Li Wang,
Ning Wang,
Fan Xiu,
Ikuya Hayashi,
Tran Anh Ngoc,
Sachie Nagae,
Samah El-Ghlban,
Shiho Shimoda,
Ahmed Abdel Aleem El Gokha,
Ibrahim El Tantawy El Sayed,
Joanna Wietrzyk,
Tsutomu Inokuchi
Affiliations
Elkhabiry Shaban
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
Marta Świtalska
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, R. Weigla Street, 53-114 Wroclaw, Poland
Li Wang
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
Ning Wang
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
Fan Xiu
Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
Ikuya Hayashi
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
Tran Anh Ngoc
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
Sachie Nagae
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
Samah El-Ghlban
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
Shiho Shimoda
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
Ahmed Abdel Aleem El Gokha
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom 32511, Egypt
Ibrahim El Tantawy El Sayed
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
Joanna Wietrzyk
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, R. Weigla Street, 53-114 Wroclaw, Poland
Tsutomu Inokuchi
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
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.
