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Structure–antitumor activity relationship of hybrid acetogenins focusing on connecting groups between heterocycles and the linker moiety† † Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2ra02399g

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. The in vivo active 1-methylpyrazole-5-sulfonamide analog of acetogenins was obtained by the structure–antitumor activity relationship, focusing on the connecting groups between the heterocycle and the linker.

SUBMITTER: Ohta K

PROVIDER: S-EPMC9131733 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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