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Updated: Sep 20, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Structure-antitumor activity relationship of hybrid acetogenins focusing on connecting groups between heterocycles
Kaito Ohta1, Tetsuya Fushimi2, Mutsumi Okamura3
1Kyoto Pharmaceutical University 1 Misasagi-Shichono-cho, Yamashina-ku Kyoto 607-8412 Japan kojima@mb.kyoto-phu.ac.jp.
Abstract:
We studied hybrid molecules of annonaceous acetogenins and mitochondrial complex I-inhibiting insecticides to develop a novel anticancer agent. A structure-antitumor activity relationship study focusing on the connecting groups between the heterocycles and the linker moiety bearing the tetrahydrofuran moiety was conducted. Eleven hybrid acetogenins with 1-methylpyrazole instead of γ-lactone were synthesized and their growth inhibitory activities against 39 human cancer cell lines were evaluated. The nitrogen atom at the 2'-position of the linker moiety was essential for inhibiting cancer growth. The 1-methylpyrazole-5-sulfonamide analog showed potent growth inhibition of NCI-H23, a human lung cancer cell line, in a xenograft mouse assay without critical toxicity. Hence, the results of this study may pave the way for the development of novel anticancer agents, with both selective and broad anticancer activities.
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