|
|
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result sql = Cytotoxicity of the novel glutathione-activated thiopurine prodrugs cis-AVTP [cis-6-(2-acetylvinylthio)purine] and trans-AVTG [trans-6-(2-acetylvinylthio)guanine] results from the National Cancer Institute's anticancer drug screen.
Cytotoxicity of the novel glutathione-activated thiopurine prodrugs cis-AVTP [cis-6-(2-acetylvinylthio)purine] and trans-AVTG [trans-6-(2-acetylvinylthio)guanine] results from the National Cancer Institute's anticancer drug screen.char = c;code = 99
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char = -;code = 45
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char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
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char = c;code = 99
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 6;code = 54
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char = M;code = 77
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 6;code = 54
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char = T;code = 84
char = G;code = 71
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char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
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char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = M;code = 77
char = P;code = 80
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = T;code = 84
char = G;code = 71
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = h;code = 104
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char = g;code = 103
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = -;code = 45
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
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char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = m;code = 109
char = e;code = 101
char = l;code = 108
char = a;code = 97
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char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
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char = c;code = 99
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = s;code = 115
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char = A;code = 65
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char = T;code = 84
char = G;code = 71
char = ,;code = 44
char = ;code = 32
char = w;code = 119
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char = e;code = 101
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char = a;code = 97
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char = A;code = 65
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char = T;code = 84
char = G;code = 71
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char = w;code = 119
char = a;code = 97
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char = o;code = 111
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char = e;code = 101
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char = f;code = 102
char = e;code = 101
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char = c;code = 99
char = i;code = 105
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char = A;code = 65
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char = T;code = 84
char = P;code = 80
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char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = ;code = 32
char = I;code = 73
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char = e;code = 101
char = r;code = 114
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char = s;code = 115
char = t;code = 116
char = i;code = 105
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char = y;code = 121
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char = e;code = 101
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char = u;code = 117
char = s;code = 115
char = i;code = 105
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char = a;code = 97
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char = t;code = 116
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char = g;code = 103
char = o;code = 111
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char = i;code = 105
char = t;code = 116
char = h;code = 104
char = m;code = 109
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = M;code = 77
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
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char = a;code = 97
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char = a;code = 97
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char = o;code = 111
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char = g;code = 103
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char = l;code = 108
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char = c;code = 99
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char = p;code = 112
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char = u;code = 117
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char = d;code = 100
char = s;code = 115
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char = i;code = 105
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char = e;code = 101
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char = a;code = 97
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char = a;code = 97
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char = e;code = 101
char = ,;code = 44
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char = c;code = 99
char = y;code = 121
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char = o;code = 111
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char = t;code = 116
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char = f;code = 102
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char = b;code = 98
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char = t;code = 116
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char = i;code = 105
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char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
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char = T;code = 84
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char = g;code = 103
char = a;code = 97
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = N;code = 78
char = S;code = 83
char = C;code = 67
char = ;code = 32
char = 3;code = 51
char = 4;code = 52
char = 8;code = 56
char = 4;code = 52
char = 0;code = 48
char = 1;code = 49
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char = b;code = 98
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char = y;code = 121
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char = H;code = 72
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char = o;code = 111
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char = a;code = 97
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char = c;code = 99
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char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
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char = a;code = 97
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char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
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char = e;code = 101
char = x;code = 120
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char = i;code = 105
char = b;code = 98
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char = a;code = 97
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char = a;code = 97
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char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
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result sql = cis-6-(2-Acetylvinylthio)purine (cis-AVTP) and trans-6-(2-acetylvinylthio)guanine (trans-AVTG) are glutathione-activated prodrugs of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), respectively. Previously, we showed that the prodrugs exhibited less in vivo toxicity in mice than did 6-TG, whereas their in vitro cytotoxicity in two renal cell carcinoma cell lines was comparable with or better than that of their respective thiopurines. To determine whether differences in sensitivity exist among different tissue types toward treatment with cis-AVTP and trans-AVTG, the cytotoxicity of the prodrugs was assessed in the National Cancer Institute's anticancer screening program, and the results were compared with the cytotoxicities of 6-MP and 6-TG obtained in the same screen. The results show that cis-AVTP was more cytotoxic than or equally cytotoxic as 6-MP. Similarly, trans-AVTG was in general more cytotoxic than 6-TG. Both prodrugs exhibited high growth-inhibitory activities in leukemic cells and melanoma cells. However, cis-AVTP was more effective against renal cancer cells than trans-AVTG, whereas trans-AVTG was more effective than cis-AVTP against ovarian cancer cells. Interestingly, analyses using the pattern-recognition algorithm COMPARE revealed that among all compounds in the database, the cytotoxic activity of both cis-AVTP and trans-AVTG correlated best with that of another thiopurine conjugate, NSC 348401 (6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)thio]-9H-purin-2-amine). Collectively, the results show that cis-AVTP and trans-AVTG exhibit both distinct and similar cytotoxicities toward different histotypes. Further investigations into the mechanisms responsible for these differences are warranted.
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result sql = Cytotoxicity of the novel glutathione-activated thiopurine prodrugs cis-AVTP [cis-6-(2-acetylvinylthio)purine] and trans-AVTG [trans-6-(2-acetylvinylthio)guanine] results from the National Cancer Institute's anticancer drug screen.
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char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = w;code = 119
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = C;code = 67
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = t;code = 116
char = e;code = 101
char = ';code = 39
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = M;code = 77
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = t;code = 116
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = M;code = 77
char = P;code = 80
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = 6;code = 54
char = -;code = 45
char = T;code = 84
char = G;code = 71
char = .;code = 46
char = ;code = 32
char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = u;code = 117
char = k;code = 107
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = g;code = 103
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = m;code = 109
char = ;code = 32
char = C;code = 67
char = O;code = 79
char = M;code = 77
char = P;code = 80
char = A;code = 65
char = R;code = 82
char = E;code = 69
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = P;code = 80
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = -;code = 45
char = A;code = 65
char = V;code = 86
char = T;code = 84
char = G;code = 71
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = p;code = 112
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = j;code = 106
char = u;code = 117
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = N;code = 78
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char = i;code = 105
char = n;code = 110
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char = ;code = 32
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char = -;code = 45
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char = e;code = 101
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char = h;code = 104
char = a;code = 97
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char = ;code = 32
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char = s;code = 115
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char = ;code = 32
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char = ;code = 32
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char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
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result sql = cis-6-(2-Acetylvinylthio)purine (cis-AVTP) and trans-6-(2-acetylvinylthio)guanine (trans-AVTG) are glutathione-activated prodrugs of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), respectively. Previously, we showed that the prodrugs exhibited less in vivo toxicity in mice than did 6-TG, whereas their in vitro cytotoxicity in two renal cell carcinoma cell lines was comparable with or better than that of their respective thiopurines. To determine whether differences in sensitivity exist among different tissue types toward treatment with cis-AVTP and trans-AVTG, the cytotoxicity of the prodrugs was assessed in the National Cancer Institute's anticancer screening program, and the results were compared with the cytotoxicities of 6-MP and 6-TG obtained in the same screen. The results show that cis-AVTP was more cytotoxic than or equally cytotoxic as 6-MP. Similarly, trans-AVTG was in general more cytotoxic than 6-TG. Both prodrugs exhibited high growth-inhibitory activities in leukemic cells and melanoma cells. However, cis-AVTP was more effective against renal cancer cells than trans-AVTG, whereas trans-AVTG was more effective than cis-AVTP against ovarian cancer cells. Interestingly, analyses using the pattern-recognition algorithm COMPARE revealed that among all compounds in the database, the cytotoxic activity of both cis-AVTP and trans-AVTG correlated best with that of another thiopurine conjugate, NSC 348401 (6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)thio]-9H-purin-2-amine). Collectively, the results show that cis-AVTP and trans-AVTG exhibit both distinct and similar cytotoxicities toward different histotypes. Further investigations into the mechanisms responsible for these differences are warranted.
Publication: Drug Metab. Dispos. 2004 Mar ;32(3)::321-7.
Publication Date: 2004 Mar
Study Author(s): Gunnarsdottir, Sjofn;Elfarra, Adnan A;
Institution: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Shortcut link to this study:
Publication Date: 2004 Mar
Study Author(s): Gunnarsdottir, Sjofn;Elfarra, Adnan A;
Institution: Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Shortcut link to this study:
cis-6-(2-Acetylvinylthio)purine (cis-AVTP) and trans-6-(2-acetylvinylthio)guanine (trans-AVTG) are glutathione-activated prodrugs of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), respectively. Previously, we showed that the prodrugs exhibited less in vivo toxicity in mice than did 6-TG, whereas their in vitro cytotoxicity in two renal cell carcinoma cell lines was comparable with or better than that of their respective thiopurines. To determine whether differences in sensitivity exist among different tissue types toward treatment with cis-AVTP and trans-AVTG, the cytotoxicity of the prodrugs was assessed in the National Cancer Institute's anticancer screening program, and the results were compared with the cytotoxicities of 6-MP and 6-TG obtained in the same screen. The results show that cis-AVTP was more cytotoxic than or equally cytotoxic as 6-MP. Similarly, trans-AVTG was in general more cytotoxic than 6-TG. Both prodrugs exhibited high growth-inhibitory activities in leukemic cells and melanoma cells. However, cis-AVTP was more effective against renal cancer cells than trans-AVTG, whereas trans-AVTG was more effective than cis-AVTP against ovarian cancer cells. Interestingly, analyses using the pattern-recognition algorithm COMPARE revealed that among all compounds in the database, the cytotoxic activity of both cis-AVTP and trans-AVTG correlated best with that of another thiopurine conjugate, NSC 348401 (6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)thio]-9H-purin-2-amine). Collectively, the results show that cis-AVTP and trans-AVTG exhibit both distinct and similar cytotoxicities toward different histotypes. Further investigations into the mechanisms responsible for these differences are warranted.
PMID: 14977866
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