2026-09-19T15:23:49.157742500Zhttps://opus.uleth.ca/server/oai/request
oai:opus.uleth.ca:10133/67842024-06-17T19:27:33Zcom_10133_3346com_10133_1com_10133_296col_10133_3347col_10133_298
ULethbridge OPUS Repository supervisor Golsteyn, Roy author Healy Knibb, Shannon M. author University of Lethbridge. Faculty of Arts and Science 2024-06-13T21:12:58Z 2024-06-13T21:12:58Z 2024 https://hdl.handle.net/10133/6784 This thesis investigates Canadian prairie plants as sources of natural product compounds capable of inhibiting human cell division. Natural products present an opportunity to identify novel anti-mitotic compounds to address the lack of known inhibitors for many mitotic regulatory proteins. By biology-guided fractionation, we purified the natural products anemonin from Pulsatilla nuttalliana and (+)-6-tuliposide A from Erythronium grandiflorum, and this is the first report of their anti-mitotic activities. We then conducted a comparative study between pulchelloid A (from Gaillardia aristata), anemonin and (+)-6-tuliposide A, and identified unique mitotic arrest profiles, suggesting distinct protein targets and mechanisms of action consistent with the widespread relationship between structure and function in biology. The discovery of natural product inhibitors from Canadian prairie plant species holds tremendous potential for advancing our understanding of mitotic regulation and contributes to the development of targeted treatments for precision medicine. en Canadian prairie plants anti-mitotic compounds natural product compounds cell division inhibitors mitotic arrest profiles mitotic regulation targeted treatments research Investigating the structure-function relationship of anti-mitotic natural products in Canadian prairie plants Thesis 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 URL http://localhost:4000/bitstreams/3b64e561-5218-4910-b022-f22df61e8c33/download File MD5 66a1b9809cc8b2781361cc4dd4ae3180 30325339 application/pdf HEALYKNIBB_SHANNON_MSC_2024.pdf URL http://localhost:4000/bitstreams/782affa5-60dd-40a6-87c2-ce4c1be65062/download File MD5 be7b63101640633dc04a314b353d5a29 104749 text/plain HEALYKNIBB_SHANNON_MSC_2024.pdf.txt