6-Arylamino-7-chloro-quinazoline-5,8-diones as novel cytotoxic and DNA topoisomerase inhibitory agents

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 13, 2004, Pages 3385-3388

  Park, Hyen Joo ^a   Kim, Young Shin ^a   Kim, Jin Sung ^a   Lee, Eun Jin ^a   Yi, You Jin ^a   Hwang, Hye Jin ^a   Suh, Myung Eun ^a   Ryu, Chung Kyu ^a   Lee, Sang Kook ^a  

^a Ewha Womans University   (South Korea)

Author keywords

6 Arylamino 7 chloro quinazoline 5,8 diones; Cytotoxicity; Topoisomerase inhibitor

Indexed keywords

ANTINEOPLASTIC AGENT; DNA TOPOISOMERASE; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE INHIBITOR; QUINAZOLINE DERIVATIVE;

ARTICLE; CANCER CELL CULTURE; CELL CULTURE; COLON CANCER; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVITY; DRUG MECHANISM; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; INHIBITION KINETICS; LUNG CANCER; STOMACH CANCER; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DNA TOPOISOMERASES; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 2942598298     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.04.094     Document Type: Article

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16. 2, 0.5 mM ATP, 0.5 mM dithiothreitol, 30 μg/mL bovine serum albumin (BSA)] containing 200 ng of KDNA (TOPOgen), and a solution of the test drugs were added to 1 unit of the human recombinant topo II (the amount of enzyme, which resulted in the complete decatenation of 200 ng of KDNA). After 10 min of incubation at 37°C, the reaction was stopped by addition of 5 μL of stop buffer containing the loading dye (1% sarkosyl, 0.025% bromophenol blue, 5% glycerol), and then the reaction mixture was analyzed on a 1% agarose gel by running at 40 V for 3.5 h in TBE buffer (89 mM Tris, 89 mM borate, 2 mM Na-EDTA, pH 8.3). Gels were made visible as described above for the relaxation assay. Gels were photographed, and remaining KDNA from photographic negatives was scanned and calculated the inhibition activity as mentioned above
17. 2, 0.5 mM ATP, 0.5 mM dithiothreitol, 30 μg/mL bovine serum albumin (BSA)] containing 200 ng of KDNA (TOPOgen), and a solution of the test drugs were added to 1 unit of the human recombinant topo II (the amount of enzyme, which resulted in the complete decatenation of 200 ng of KDNA). After 10 min of incubation at 37°C, the reaction was stopped by addition of 5 μL of stop buffer containing the loading dye (1% sarkosyl, 0.025% bromophenol blue, 5% glycerol), and then the reaction mixture was analyzed on a 1% agarose gel by running at 40 V for 3.5 h in TBE buffer (89 mM Tris, 89 mM borate, 2 mM Na-EDTA, pH 8.3). Gels were made visible as described above for the relaxation assay. Gels were photographed, and remaining KDNA from photographic negatives was scanned and calculated the inhibition activity as mentioned above
18. 2, 0.5 mM ATP, 0.5 mM dithiothreitol, 30 μg/mL bovine serum albumin (BSA)] containing 200 ng of KDNA (TOPOgen), and a solution of the test drugs were added to 1 unit of the human recombinant topo II (the amount of enzyme, which resulted in the complete decatenation of 200 ng of KDNA). After 10 min of incubation at 37°C, the reaction was stopped by addition of 5 μL of stop buffer containing the loading dye (1% sarkosyl, 0.025% bromophenol blue, 5% glycerol), and then the reaction mixture was analyzed on a 1% agarose gel by running at 40 V for 3.5 h in TBE buffer (89 mM Tris, 89 mM borate, 2 mM Na-EDTA, pH 8.3). Gels were made visible as described above for the relaxation assay. Gels were photographed, and remaining KDNA from photographic negatives was scanned and calculated the inhibition activity as mentioned above