dc.contributor.author | Constantinou, Andreas I. | en |
dc.contributor.author | Mehta, R. | en |
dc.contributor.author | Runyan, C. | en |
dc.contributor.author | Rao, K. | en |
dc.contributor.author | Vaughan, A. | en |
dc.contributor.author | Moon, R. | en |
dc.creator | Constantinou, Andreas I. | en |
dc.creator | Mehta, R. | en |
dc.creator | Runyan, C. | en |
dc.creator | Rao, K. | en |
dc.creator | Vaughan, A. | en |
dc.creator | Moon, R. | en |
dc.date.accessioned | 2019-11-04T12:50:23Z | |
dc.date.available | 2019-11-04T12:50:23Z | |
dc.date.issued | 1995 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/52999 | |
dc.description.abstract | Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibited topo II without inhibiting topo I. Flavonoids demonstrating potent topo I and II inhibition required hydroxyl group substitution at the C-3, C-7, C-3', and C-4' positions and also required a keto group at C-4. Additional B-ring hydroxylation enhanced flavonoid topo I inhibitory action. A C-2,C-3 double bond was also required, but when the A ring is opened, the requirement for the double bond was eliminated. Genistein has been previously reported to stabilize the covalent topo II-DNA cleavage complex and thus function as a topo II poison. All flavonoids were tested for their ability to stabilize the cleavage complex between topo I or topo II and DNA. None of the agents stabilized the topo I-DNA cleavage complex, but prunetin, quercetin, kaempferol, and apigenin stabilized the topo II DNA-complex. Competition experiments have shown that genistein-induced topo II-mediated DNA cleavage can be inhibited by myricetin, suggesting that both types of inhibitors (antagonists and poisons) interact with the same functional domain of their target enzyme. These results are of use for the selection of flavonoids that can inhibit specific topoisomerases at specific stages of the topoisomerization reaction. © 1995, American Chemical Society. All rights reserved. | en |
dc.source | Journal of natural products | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028948804&doi=10.1021%2fnp50116a009&partnerID=40&md5=e2fa1711d375c9143b5254ef0182bb80 | |
dc.subject | article | en |
dc.subject | cancer chemotherapy | en |
dc.subject | etoposide | en |
dc.subject | controlled study | en |
dc.subject | drug targeting | en |
dc.subject | enzyme activity | en |
dc.subject | teniposide | en |
dc.subject | Structure-Activity Relationship | en |
dc.subject | amsacrine | en |
dc.subject | DNA Topoisomerases, Type II | en |
dc.subject | Protein Conformation | en |
dc.subject | Support, U.S. Gov't, P.H.S. | en |
dc.subject | daidzein | en |
dc.subject | genistein | en |
dc.subject | structure activity relation | en |
dc.subject | DNA Topoisomerases, Type I | en |
dc.subject | quercetin | en |
dc.subject | dna topoisomerase (atp hydrolysing) | en |
dc.subject | dna strand breakage | en |
dc.subject | dna topoisomerase | en |
dc.subject | DNA Damage | en |
dc.subject | 3 hydroxyflavone | en |
dc.subject | 4',6,7 trihydroxyisoflavone | en |
dc.subject | 6 hydroxyflavone | en |
dc.subject | 7 hydroxyflavone | en |
dc.subject | apigenin | en |
dc.subject | Bioflavonoids | en |
dc.subject | catechin | en |
dc.subject | dna cleavage | en |
dc.subject | dna drug complex | en |
dc.subject | Electrophoresis, Agar Gel | en |
dc.subject | fisetin | en |
dc.subject | flavone derivative | en |
dc.subject | flavonoid | en |
dc.subject | galangin | en |
dc.subject | gyrase inhibitor | en |
dc.subject | Hydroxylation | en |
dc.subject | isomerism | en |
dc.subject | kaempferol | en |
dc.subject | morin | en |
dc.subject | myricetin | en |
dc.subject | phloretin | en |
dc.subject | Plasmids | en |
dc.subject | poison | en |
dc.subject | prunetin | en |
dc.title | Flavonoids as DNA topoisomerase antagonists and poisons: Structure-activity relationships | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1021/np50116a009 | |
dc.description.volume | 58 | |
dc.description.startingpage | 217 | |
dc.description.endingpage | 225 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Tradenames: vm 26, bristol myers squibb, United States | en |
dc.description.notes | vp 16, bristol myers squibb, United States | en |
dc.description.notes | Manufacturers: aldrich, United States | en |
dc.description.notes | bristol myers squibb, United States | en |
dc.description.notes | gibco, United States | en |
dc.description.notes | sigma, United States | en |
dc.description.notes | Cited By :222</p> | en |
dc.source.abbreviation | J.Nat.Prod. | en |
dc.contributor.orcid | Constantinou, Andreas I. [0000-0003-0365-1821] | |
dc.gnosis.orcid | 0000-0003-0365-1821 | |