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Anticancer activity of cytokinins: structure-activity relationship studies
Title statement Anticancer activity of cytokinins: structure-activity relationship studies [rukopis] / Jiří Voller Additional Variant Titles Protinádorová aktivita cytokininů: Studie vztahu mezi strukturou a účinkem Personal name Voller, Jiří (dissertant) Translated title Anticancer activity of cytokinins: structure-activity relationship studies Issue data 2010 Phys.des. 32 s. (50646) , 35 s. prilohy + 1 ks CD ROM Note Ved. práce Miroslav Strnad Another responsib. Strnad, Miroslav, 1958- (thesis advisor) Kovařík, Jan (opponent) Santaniello, Enzo (opponent) Mlejnek, Petr (opponent) Another responsib. Univerzita Palackého. Katedra botaniky (degree grantor) Keywords SAR * cytokinins * cancer * ortho-topolin riboside * NCI60 * SAR * cytokinins * cancer * ortho-topolin riboside * NCI60 Form, Genre disertace dissertations UDC (043.3) Country Česko Language angličtina Document kind PUBLIKAČNÍ ČINNOST Title Ph.D. Degree program Doktorský Degree program Biologie Degreee discipline Botanika book
Kvalifikační práce Downloaded Size datum zpřístupnění 130906-216137836.pdf 33 973.6 KB 24.06.2010 Call number Barcode Location Sublocation Info DIS/082 (PřF-KBO) 3134512114 PřF-Holice PřF, Knihovna Holice - sklad In-Library Use Only
A study of the relationship between the chemical structure of cytokinins and their cytotoxic effects against a panel of human cancer cell lines with diverse histopathological origins is presented. Test compounds included almost all known natural cytokinins (N = 42) and two groups of novel synthetic analogues: derivatives of N6-benzyladenosine with diverse substitutions on the benzyl ring (N = 48) and their analogues where the ribose moiety is replaced by a tetrahydropyran-2-yl or tetrahydrofuran-2-yl group (N = 34). Strong cytotoxic activity was limited to certain cytokinin ribosides and their corresponding ribotides. The anticancer activity of aromatic cytokinin ribosides can be improved by fluorination or ortho- hydroxylation of the benzyl ring. The potent anticancer activity of the natural cytokinin ortho-topolin riboside (median GI50 = 0.65 ?M) was confirmed using NCI60. Its activity pattern was distinctly different from those of standard anticancer drugs, suggesting that it has a unique mechanism of action. In comparison with standard drugs, ortho-topolin riboside showed exceptional cytotoxic activity against NCI60 cell lines with a mutated p53 tumour suppressor gene. Ortho-topolin riboside also exhibited significant anticancer activity against several tumour models in in vivo hollow fibre assays.A study of the relationship between the chemical structure of cytokinins and their cytotoxic effects against a panel of human cancer cell lines with diverse histopathological origins is presented. Test compounds included almost all known natural cytokinins (N = 42) and two groups of novel synthetic analogues: derivatives of N6-benzyladenosine with diverse substitutions on the benzyl ring (N = 48) and their analogues where the ribose moiety is replaced by a tetrahydropyran-2-yl or tetrahydrofuran-2-yl group (N = 34). Strong cytotoxic activity was limited to certain cytokinin ribosides and their corresponding ribotides. The anticancer activity of aromatic cytokinin ribosides can be improved by fluorination or ortho- hydroxylation of the benzyl ring. The potent anticancer activity of the natural cytokinin ortho-topolin riboside (median GI50 = 0.65 ?M) was confirmed using NCI60. Its activity pattern was distinctly different from those of standard anticancer drugs, suggesting that it has a unique mechanism of action. In comparison with standard drugs, ortho-topolin riboside showed exceptional cytotoxic activity against NCI60 cell lines with a mutated p53 tumour suppressor gene. Ortho-topolin riboside also exhibited significant anticancer activity against several tumour models in in vivo hollow fibre assays.
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