Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 4, 2008, Pages 1484-1489

  Dallavalle, Sabrina ^a   Gattinoni, Sonia ^a   Mazzini, Stefania ^a   Scaglioni, Leonardo ^a   Merlini, Lucio ^a   Tinelli, Stella ^b   Beretta, Giovanni L ^b   Zunino, Franco ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

Antitumor; Cytotoxic activity; Topoisomerase I; Topopyrones

Indexed keywords

ANTINEOPLASTIC AGENT; HYDROXYL GROUP; PYRONE DERIVATIVE; TOPOISOMERASE I INHIBITOR; TOPOPYRONE C; TOPOTECAN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

ANTHRAQUINONES; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; DNA; DNA TOPOISOMERASES, TYPE I; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; LUNG NEOPLASMS; PYRONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 38949212995     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.12.055     Document Type: Article

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19. 2, 15 μg/ml BSA, 0.1 mM dithiothreitol, and 640 ng of human recombinant enzyme (full length topoisomerase I) for 30 min at 37 °C. Reactions were stopped by adding 0.5% SDS and 0.3 mg/ml of proteinase K for 45 min at 42 °C. After precipitation, DNA was resuspended in denaturing buffer (80% formamide, 10 mM NaOH, 0.01 M EDTA, and 1 mg/ml dyes) before loading on a denaturing 8% polyacrylamide gel in TBE buffer.
20. 2, 0.5 μg/ml BSA, 0.1 mM EDTA, 150 mM KCl in the presence of purified protein and with 1, 10, and 50 μM of compound. Samples were incubated for 30 min at 37 °C and then stopped by adding 0.5% SDS and 0.3 mg/ml proteinase K at 42 °C for 45 min. Plasmid relaxation was analyzed on 0.8% agarose gel followed by ethidium bromide staining.