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• W3136456830 endingPage "104840" @default.
• W3136456830 startingPage "104840" @default.
• W3136456830 abstract "To further explore the research of novel PARP-1 inhibitors, we designed and synthesized a series of novel amide PARP-1 inhibitors based on our previous research. Most compounds displayed certain antitumor activities against four tumor cell lines (A549, HepG2, HCT-116, and MCF-7). Specifically, the candidate compound R8e possessed strong anti-proliferative potency toward A549 cells with the IC50 value of 2.01 μM. Compound R8e had low toxicity to lung cancer cell line. And the in vitro enzyme inhibitory activity of compound R8e was better than rucaparib. Molecular docking studies provided a rational binding model of compound R8e in complex with rucaparib. The following cell cycle and apoptosis assays revealed that compound R8e could arrest cell cycle in the S phase and induce cell apoptosis. Western blot analysis further showed that compound R8e could effectively inhibit the PAR's biosynthesis and was more effective than rucaparib. Overall, based on the biological activity evaluation, compound R8e could be a potential lead compound for further developing novel amide PARP-1 inhibitors." @default.
• W3136456830 created "2021-03-29" @default.
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• W3136456830 date "2021-06-01" @default.
• W3136456830 modified "2023-10-06" @default.
• W3136456830 title "Novel 4,5-dihydrospiro[benzo[c]azepine-1,1′-cyclohexan]-3(2H)-one derivatives as PARP-1 inhibitors: Design, synthesis and biological evaluation" @default.
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• W3136456830 doi "https://doi.org/10.1016/j.bioorg.2021.104840" @default.
• W3136456830 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33780687" @default.
• W3136456830 hasPublicationYear "2021" @default.
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