|
|
char = E;code = 69
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char = c;code = 99
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char = r;code = 114
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char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
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char = e;code = 101
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char = c;code = 99
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char = l;code = 108
char = a;code = 97
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
char = ;code = 32
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char = r;code = 114
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char = z;code = 122
char = a;code = 97
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char = e;code = 101
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char = l;code = 108
char = ;code = 32
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char = a;code = 97
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char = i;code = 105
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char = m;code = 109
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result sql = Electron-deficient DNA-intercalating agents as antitumor drugs: aza analogues of the experimental clinical agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.
Electron-deficient DNA-intercalating agents as antitumor drugs: aza analogues of the experimental clinical agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.char = A;code = 65
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char = ;code = 32
char = a;code = 97
char = z;code = 122
char = a;code = 97
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char = i;code = 105
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char = p;code = 112
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char = e;code = 101
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char = d;code = 100
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char = g;code = 103
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char = N;code = 78
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char = i;code = 105
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char = -;code = 45
char = c;code = 99
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char = A;code = 65
char = C;code = 67
char = A;code = 65
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char = r;code = 114
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char = l;code = 108
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char = i;code = 105
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char = ;code = 32
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = );code = 41
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = s;code = 115
char = y;code = 121
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char = i;code = 105
char = z;code = 122
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char = T;code = 84
char = h;code = 104
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char = e;code = 101
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char = c;code = 99
char = o;code = 111
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char = s;code = 115
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char = d;code = 100
char = ;code = 32
char = D;code = 68
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = b;code = 98
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char = a;code = 97
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char = f;code = 102
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char = s;code = 115
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char = i;code = 105
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char = t;code = 116
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char = m;code = 109
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char = d;code = 100
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char = s;code = 115
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char = b;code = 98
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char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = g;code = 103
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char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = o;code = 111
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char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
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char = t;code = 116
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char = t;code = 116
char = o;code = 111
char = x;code = 120
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char = ;code = 32
char = a;code = 97
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char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = P;code = 80
char = 3;code = 51
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char = 8;code = 56
char = ;code = 32
char = l;code = 108
char = e;code = 101
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char = k;code = 107
char = e;code = 101
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char = a;code = 97
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char = i;code = 105
char = t;code = 116
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char = .;code = 46
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char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = o;code = 111
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char = h;code = 104
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
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char = t;code = 116
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char = o;code = 111
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char = c;code = 99
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char = h;code = 104
char = a;code = 97
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char = D;code = 68
char = A;code = 65
char = C;code = 67
char = A;code = 65
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result sql = A series of azaacridine (benzonaphthyridine) analogues of the drug N-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (DACA) (currently in clinical trial) were synthesized. These compounds showed DNA binding affinities similar to that of DACA, as determined by the fluorometric ethidium displacement assay, but were generally less potent cytotoxins against P388 leukemia in vitro. The only compounds showing higher cytotoxicity than DACA were analogues with nitro substituents at the (acridine) 1-position; by analogy with the 1-nitroacridine nitracrine, these compounds probably undergo reductive metabolism. The only azaacridine to show significant in vivo antileukemic activity was benzo[b][1,5]naphthyridine-6-carboxamide. A possible reason for the unexpectedly low activity of these compounds (given the wide acceptability of substituents in DACA) may be their much lower lipophilicities, which are likely to result in lower rates of cell uptake.
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result sql = Electron-deficient DNA-intercalating agents as antitumor drugs: aza analogues of the experimental clinical agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.
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char = d;code = 100
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char = ;code = 32
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char = o;code = 111
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char = s;code = 115
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char = x;code = 120
char = p;code = 112
char = e;code = 101
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char = e;code = 101
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char = c;code = 99
char = t;code = 116
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char = v;code = 118
char = i;code = 105
char = t;code = 116
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char = ;code = 32
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char = m;code = 109
char = p;code = 112
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char = u;code = 117
char = n;code = 110
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result sql = A series of azaacridine (benzonaphthyridine) analogues of the drug N-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (DACA) (currently in clinical trial) were synthesized. These compounds showed DNA binding affinities similar to that of DACA, as determined by the fluorometric ethidium displacement assay, but were generally less potent cytotoxins against P388 leukemia in vitro. The only compounds showing higher cytotoxicity than DACA were analogues with nitro substituents at the (acridine) 1-position; by analogy with the 1-nitroacridine nitracrine, these compounds probably undergo reductive metabolism. The only azaacridine to show significant in vivo antileukemic activity was benzo[b][1,5]naphthyridine-6-carboxamide. A possible reason for the unexpectedly low activity of these compounds (given the wide acceptability of substituents in DACA) may be their much lower lipophilicities, which are likely to result in lower rates of cell uptake.
Publication: J. Med. Chem. 1994 Mar 4 ;37(5)::593-7.
Publication Date: 1994 Mar 4
Study Author(s): Chen, Q;Deady, L W;Baguley, B C;Denny, W A;
Institution: Department of Chemistry, La Trobe University, Bundoora, Victoria, Australia.
Shortcut link to this study:
Publication Date: 1994 Mar 4
Study Author(s): Chen, Q;Deady, L W;Baguley, B C;Denny, W A;
Institution: Department of Chemistry, La Trobe University, Bundoora, Victoria, Australia.
Shortcut link to this study:
A series of azaacridine (benzonaphthyridine) analogues of the drug N-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (DACA) (currently in clinical trial) were synthesized. These compounds showed DNA binding affinities similar to that of DACA, as determined by the fluorometric ethidium displacement assay, but were generally less potent cytotoxins against P388 leukemia in vitro. The only compounds showing higher cytotoxicity than DACA were analogues with nitro substituents at the (acridine) 1-position; by analogy with the 1-nitroacridine nitracrine, these compounds probably undergo reductive metabolism. The only azaacridine to show significant in vivo antileukemic activity was benzo[b][1,5]naphthyridine-6-carboxamide. A possible reason for the unexpectedly low activity of these compounds (given the wide acceptability of substituents in DACA) may be their much lower lipophilicities, which are likely to result in lower rates of cell uptake.
PMID: 8126699
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