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A specific dispiropiperazine derivative that arrests cell cycle, induces apoptosis, necrosis and DNA damage

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dc.contributor.authorLiu, Victor P.
dc.contributor.authorLi, Wai-Ming
dc.contributor.authorLofroth, Jack
dc.contributor.authorZeb, Mehreen
dc.contributor.authorPatrick, Brian O.
dc.contributor.authorBott, Tina
dc.contributor.authorLee, Chow H.
dc.date.accessioned2023-11-22T22:21:59Z
dc.date.available2023-11-22T22:21:59Z
dc.date.issued2023
dc.description.abstractDispiropiperazine compounds are a class of molecules known to confer biological activity, but those that have been studied as cell cycle regulators are few in number. Here, we report the characterization and synthesis of two dispiropiperazine derivatives: the previously synthesized spiro[2′,3]- bis(acenaphthene-1′-one)perhydrodipyrrolo-[1,2-a:1,2-d]-pyrazine (SPOPP-3, 1), and its previously undescribed isomer, spiro[2′,5′] bis(acenaphthene-1′-one)perhydrodipyrrolo-[1,2-a:1,2-d]-pyrazine (SPOPP-5, 2). SPOPP-3 (1), but not SPOPP-5 (2), was shown to have anti proliferative activity against a panel of 18 human cancer cell lines with IC50 values ranging from 0.63 to 13 μM. Flow cytometry analysis revealed that SPOPP-3 (1) was able to arrest cell cycle at the G2/M phase in SW480 human cancer cells. Western blot analysis further confirmed the cell cycle arrest is in the M phase. In addition, SPOPP-3 (1) was shown to induce apoptosis, necrosis, and DNA damage as well as disrupt mitotic spindle positioning in SW480 cells. These results warrant further investigation of SPOPP-3 (1) as a novel anti-cancer agent, particularly for its potential ability to sensitize cancer cells for radiation induced cell death, enhance cancer immunotherapy, overcome apoptosis-related drug resistance and for possible use in synthetic lethality cancer treatments.
dc.identifier.citationLiu, V. P., Li, W. M., Lofroth, J., Zeb, M., Patrick, B. O., Bott, T. M., & Lee, C. H. (2023). A specific dispiropiperazine derivative that arrests cell cycle, induces apoptosis, necrosis and DNA damage. Scientific reports, 13(1), 8674. https://doi.org/10.1038/s41598-023-35927-6
dc.identifier.doihttps://doi.org/10.1038/s41598-023-35927-6
dc.identifier.urihttps://hdl.handle.net/20.500.14078/3259
dc.language.isoen
dc.rightsAttribution (CC BY)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDispiropiperazine compounds
dc.subjectdispiropiperazine derivatives
dc.subjectcancer
dc.titleA specific dispiropiperazine derivative that arrests cell cycle, induces apoptosis, necrosis and DNA damageen
dc.typeArticle

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