char = S;code = 83 char = t;code = 116 char = r;code = 114 char = u;code = 117 char = c;code = 99 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = -;code = 45 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 = s;code = 115 char = t;code = 116 char = u;code = 117 char = d;code = 100 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = z;code = 122 char = o;code = 111 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = .;code = 46 result sql = Structure-activity study of pentamidine analogues as antiprotozoal agents.
Structure-activity study of pentamidine analogues as antiprotozoal agents.char = D;code = 68 char = i;code = 105 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = 1;code = 49 char = ;code = 32 char = (;code = 40 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = );code = 41 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 6;code = 54 char = 5;code = 53 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = (;code = 40 char = 2;code = 50 char = -;code = 45 char = 6;code = 54 char = 6;code = 54 char = );code = 41 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = z;code = 122 char = o;code = 111 char = a;code = 97 char = l;code = 108 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 = 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 = T;code = 84 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = ;code = 32 char = b;code = 98 char = r;code = 114 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = i;code = 105 char = ;code = 32 char = r;code = 114 char = h;code = 104 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = e;code = 101 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = P;code = 80 char = l;code = 108 char = a;code = 97 char = s;code = 115 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = i;code = 105 char = u;code = 117 char = m;code = 109 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = l;code = 108 char = c;code = 99 char = i;code = 105 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = u;code = 117 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 = L;code = 76 char = e;code = 101 char = i;code = 105 char = s;code = 115 char = h;code = 104 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = a;code = 97 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 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 = 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 = m;code = 109 char = a;code = 97 char = m;code = 109 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = i;code = 105 char = a;code = 97 char = n;code = 110 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 = D;code = 68 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ;code = 32 char = 3;code = 51 char = 2;code = 50 char = ,;code = 44 char = ;code = 32 char = 6;code = 54 char = 4;code = 52 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 6;code = 54 char = 6;code = 54 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 = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = t;code = 116 char = e;code = 101 char = n;code = 110 char = c;code = 99 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = e;code = 101 char = q;code = 113 char = u;code = 117 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = g;code = 103 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = s;code = 115 char = o;code = 111 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = l;code = 108 char = ;code = 32 char = (;code = 40 char = I;code = 73 char = C;code = 67 char = (;code = 40 char = 5;code = 53 char = 0;code = 48 char = );code = 41 char = ;code = 32 char = =;code = 61 char = ;code = 32 char = 4;code = 52 char = ;code = 32 char = n;code = 110 char = M;code = 77 char = );code = 41 char = .;code = 46 char = ;code = 32 char = N;code = 78 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 = g;code = 103 char = e;code = 101 char = n;code = 110 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = (;code = 40 char = 2;code = 50 char = -;code = 45 char = 4;code = 52 char = ,;code = 44 char = ;code = 32 char = 1;code = 49 char = 2;code = 50 char = ,;code = 44 char = ;code = 32 char = 2;code = 50 char = 7;code = 55 char = ,;code = 44 char = ;code = 32 char = 3;code = 51 char = 0;code = 48 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 6;code = 54 char = 4;code = 52 char = -;code = 45 char = 6;code = 54 char = 6;code = 54 char = );code = 41 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = a;code = 97 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 = P;code = 80 char = .;code = 46 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = l;code = 108 char = c;code = 99 char = i;code = 105 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = u;code = 117 char = m;code = 109 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = e;code = 101 char = m;code = 109 char = i;code = 105 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = (;code = 40 char = I;code = 73 char = C;code = 67 char = (;code = 40 char = 5;code = 53 char = 0;code = 48 char = );code = 41 char = ;code = 32 char = =;code = 61 char = ;code = 32 char = 6;code = 54 char = ;code = 32 char = n;code = 110 char = M;code = 77 char = );code = 41 char = .;code = 46 char = ;code = 32 char = E;code = 69 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = t;code = 116 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 = (;code = 40 char = 1;code = 49 char = 2;code = 50 char = ,;code = 44 char = ;code = 32 char = 3;code = 51 char = 2;code = 50 char = ,;code = 44 char = ;code = 32 char = 3;code = 51 char = 3;code = 51 char = ,;code = 44 char = ;code = 32 char = 4;code = 52 char = 4;code = 52 char = ,;code = 44 char = ;code = 32 char = 5;code = 53 char = 9;code = 57 char = ,;code = 44 char = ;code = 32 char = 6;code = 54 char = 2;code = 50 char = ,;code = 44 char = ;code = 32 char = 6;code = 54 char = 4;code = 52 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 6;code = 54 char = 6;code = 54 char = );code = 41 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 = e;code = 101 char = q;code = 113 char = u;code = 117 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = l;code = 108 char = e;code = 101 char = i;code = 105 char = s;code = 115 char = h;code = 104 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = a;code = 97 char = l;code = 108 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 = t;code = 116 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = ;code = 32 char = 1;code = 49 char = ;code = 32 char = (;code = 40 char = I;code = 73 char = C;code = 67 char = (;code = 40 char = 5;code = 53 char = 0;code = 48 char = );code = 41 char = ;code = 32 char = =;code = 61 char = ;code = 32 char = 1;code = 49 char = .;code = 46 char = 8;code = 56 char = ;code = 32 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = M;code = 77 char = );code = 41 char = .;code = 46 char = ;code = 32 char = S;code = 83 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = e;code = 101 char = r;code = 114 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 = m;code = 109 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = a;code = 97 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 = 1;code = 49 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = v;code = 118 char = o;code = 111 char = ,;code = 44 char = ;code = 32 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = 2;code = 50 char = /;code = 47 char = 4;code = 52 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = m;code = 109 char = a;code = 97 char = l;code = 108 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 = a;code = 97 char = c;code = 99 char = u;code = 117 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = a;code = 97 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = i;code = 105 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = a;code = 97 char = z;code = 122 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = 6;code = 54 char = 6;code = 54 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 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 = ;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 = e;code = 101 char = r;code = 114 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = s;code = 115 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 = e;code = 101 char = x;code = 120 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 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 = a;code = 97 char = n;code = 110 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 = s;code = 115 char = e;code = 101 char = l;code = 108 char = e;code = 101 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 = 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 = T;code = 84 char = .;code = 46 char = ;code = 32 char = b;code = 98 char = .;code = 46 char = ;code = 32 char = r;code = 114 char = h;code = 104 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = e;code = 101 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = P;code = 80 char = .;code = 46 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = l;code = 108 char = c;code = 99 char = i;code = 105 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = u;code = 117 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 = L;code = 76 char = .;code = 46 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = n;code = 110 char = o;code = 111 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = b;code = 98 char = i;code = 105 char = n;code = 110 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 = h;code = 104 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = y;code = 121 char = p;code = 112 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = o;code = 111 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = c;code = 99 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = v;code = 118 char = o;code = 111 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC(50) = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC(50) = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC(50) = 1.8 microM). Several congeners were more active than 1 in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.
Publication: J. Med. Chem. 2009 Apr 9 ;52(7)::2016-35. :doi: 10.1021/jm801547t.
Publication Date: 2009 Apr 9
Study Author(s): Bakunova, Svetlana M;Bakunov, Stanislav A;Patrick, Donald A;Kumar, E V K Suresh;Ohemeng, Kwasi A;Bridges, Arlene S;Wenzler, Tanja;Barszcz, Todd;Jones, Susan Kilgore;Werbovetz, Karl A;Brun, Reto;Tidwell, Richard R;
Institution: Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Shortcut link to this study:
Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC(50) = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC(50) = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC(50) = 1.8 microM). Several congeners were more active than 1 in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.
PMID: 19267462