Table 1.
C(2)/C(5)/C(6) amidine analogs and cytotoxicity
Compound | 2R | 5R | X | uPA IC50 μM | tPA IC50 μM | Plasmin IC50 μM | Trypsin IC50 μM | Cytoxicity |
---|---|---|---|---|---|---|---|---|
amiloride | acylguanidine (H2N)2C=NC(O)– | NH2 | Cl | 7 | 220 | >250 | >250 | 50% cytotoxic at 250μM by 24h |
7 amidox-Am-C(5)-Gly-OBn | amidoxime H2NC(NOH)- | -NHCH2CO2Bn | Cl | 74 | 200 | >250 | >250 | Not cytotoxic |
8 amidox-Am-C(5)-Gly-OH | amidoxime H2NC(NOH)- | -NHCH2CO2H | Cl | 231 | >250 | >250 | >250 | Not cytotoxic |
8-H dechloro-amidox-Am-C(5)-Gly-OH | amidoxime H2NC(NOH)- | -NHCH2CO2H | H | 279 | >250 | 230 | >250 | Not cytotoxic |
11 amidine-Am-C(5)-Gly-OBn | amidine H2NC(NH)- | -NHCH2CO2Bn | Cl | 4 | 200 | >250 | >250 | 50% cytotoxic at 250μM by 72h |
2 amidine-Am-C(5)-Gly-OH | amidine H2NC(NH)- | -NHCH2CO2H | Cl | 237 | >250 | >250 | >250 | Not cytotoxic |
2-H dechloro- amidine-Am-C(5)-Gly-OH | amidine H2NC(NH)- | -NHCH2CO2H | H | 212 | >250 | >250 | >250 | Not cytotoxic |
12 amide-Am-C(5)-Gly-OBn | carboxamide H2NC(O)- | -NHCH2CO2Bn | Cl | 69 | >250 | >150 | >250 | Not cytotoxic |
14 Am-C(5)-Gly-OBn | acyl guanidine (H2N)2C=NC(O)- | -NHCH2CO2Bn | Cl | 3 | >190 | >250 | >250 | 50% cytotoxic at 100μM by 24h |
1 Am-C(5)-Gly-OH | acyl guanidine (H2N)2C=NC(O)- | -NHCH2CO2H | Cl | 17 | >250 | >250 | >250 | Not cytotoxic |
1-H dechloro-Am-C(5)-Gly-0H | acyl guanidine (H2N)2C=NC(O)- | -NHCH2CO2H | H | 47 | >250 | >250 | >250 | Not cytotoxic |