TABLE 3.
Cytotoxicity profile for 1,6-naphthyridine and 7,8-dihydroisoquinoline representatives
| Cell line | CC50 (μM)
|
||||
|---|---|---|---|---|---|
| Controla | A1 | B1 | B2 | B3 | |
| MRC-5b | >3,921 | 8 | 90 | 26 | 255 |
| HFFb | >102 | 31 | >23 | 26 | >28 |
| MA-104c | >444 | 6.2 ± 0.3 | 93.1 ± 8.5 | 63.6 ± 1.3 | 91.8 ± 0.2 |
| MDCKc | >410 | 17.4 ± 2.5 | >282 | 35 ± 5.1 | >344 |
| A549c | 125.4 ± 16.5 | 15.6 ± 3.1 | 225.6 ± 2.3 | 95.4 ± 3.1 | 116 ± 10.2 |
| Hs68d | 54.2 ± 4.9 | 5.9 ± 2.1 | 175 | 15 ± 1.6 | 85 |
| Verod | 31.2 ± 2.5 | 1 | >282 | 20 | 170 |
| Hs68e | >392 | >312 | >282 | >318 | >344 |
| Veroe | >100 | NDg | >282 | 80 | 344 |
| CEM-SSf | >2.0 | 3 | 87 | 24 | 71 |
| PBMCf | >1.1 | 19 | >180 | 23 | 255 |
Controls: GCV for MRC-5, HFF, and Hs68 cells; ribavirin for MDCK cells; HPMPA for A549 cells; acyclovir for MA-104 and Vero cells; dideoxycytosine for CEM-SS cells; and zidovudine for PBMC.
Visual assessment on MRC-5 and HFF stationary cells (31, 37) was performed in six separate experiments. On a one to four-plus basis of scoring the cytopathology, no variation around the reported values was noticed.
Neutral red uptake on stationary cells (15, 30). MA-104, MDCK, and A549 cells were observed microscopically for drug-induced morphological changes by using seven concentrations of test compound in duplicate.
Thymidine uptake on exponentially growing Hs68 and Vero cells as described in Materials and Methods.
WST-1 cell proliferating agent on exponentially growing Hs68 and Vero cells as described in Materials and Methods.
XTT cell proliferating agent method (4). Experiments were performed in triplicate. Standard deviation was less than 15%.
ND, not determined.