Synthesis and Cytotoxic Activity of N,N′-(Arylmethylene)bisamides

Junichi Uenishi; Hirokazu Hirano; Tsuyoshi Ueda; Naoyuki Hoshiya; Hiromi Ii; Tatsuhiro Yoshiki

doi:10.1055/s-0034-1380437

Synthesis, Table of Contents

Synthesis 2015; 47(19): 2976-2984
DOI: 10.1055/s-0034-1380437

paper

Synthesis and Cytotoxic Activity of N,N′-(Arylmethylene)bisamides

Junichi Uenishi*

^aDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: juenishi@mb.kyoto-phu.ac.jp

,

Hirokazu Hirano

^aDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: juenishi@mb.kyoto-phu.ac.jp

,

Tsuyoshi Ueda

^aDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: juenishi@mb.kyoto-phu.ac.jp

,

Naoyuki Hoshiya

^aDepartment of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: juenishi@mb.kyoto-phu.ac.jp

,

Hiromi Ii

^bDepartment of Clinical Oncology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: yoshiki@mb.kyoto-phu.ac.jp

,

Tatsuhiro Yoshiki*

^bDepartment of Clinical Oncology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan Email: yoshiki@mb.kyoto-phu.ac.jp

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Abstract

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Abstract

N,N′-(Arylmethylene)bisamides were prepared by an acid-catalyzed reaction of arylaldehydes with cinnamamide or acrylamides. The reaction was carried out in refluxing toluene for a few hours, and simple collection of the precipitate gave the desired products. The bisamides were designed as cytotoxic molecules based on the structure of the potently cytotoxic marine natural product (–)-zampanolide. The activities of the bisamides against two cancer cell lines were evaluated, and several compounds were found to show medium potency with IC₅₀ values in the lower micromolar level.

Key words

amides - medicinal chemistry - cytotoxins - condensation - bisamides

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References

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