Table 11.
Effects of synthesized compounds on mammary tumorigenesis.
| Comp. | Dose | log D7.4 a | Tumor Latency | Tumor Burden | Tumor Volume | Rat PPB b |
Rat CL c |
BIO d | MFD e (5 days) |
WL after MFD f (day 1, mg) g |
|---|---|---|---|---|---|---|---|---|---|---|
| (mg/kg) | (week) | (week) | (mm3) | (%free) | in vivo | (mg/kg) | (day 5, mg) h | |||
| 3DPQ-1 | 5 | 1.94 ‡,‖ | 9 * | 3.38 ± 0.31 i,*,†,‖ | 1.09 ± 0.23 *,†,‡,‖ | 1.33 ‡,‖ | 60 ‡,‖ | 91 | 1000 | 310.34 ± 0.34 i |
| 50 | 12 *,† | 2.04 ± 0.35 *,†,§,┴ | 0.68 ± 0.35 *,†,§,┴ | 1.22 §,┴ | 69 §,┴ | 94 | 300.23 ± 0.62 | |||
| 3DPQ-2 | 5 | 1.99 ‡,‖ | 9 * | 3.34 ± 0.57 *,†,‖ | 0.96 ± 0.41 *,†,‡,‖ | 1.15 ‡,‖ | 59 ‡,‖ | 92 | 1000 | 305.03 ± 0.66 |
| 50 | 12 *,† | 1.98 ± 0.45 *,†,§,┴ | 0.69 ± 0.23 *,†,§,┴ | 1.24 §,┴ | 64 §,┴ | 94 | 300.43 ± 0.65 | |||
| 3DPQ-3 | 5 | 2.07 ‡,‖ | 12 *,†,‡ | 2.18 ± 0.69 *,†,‡,‖ | 0.78 ± 0.43 *,†,‡,‖ | 1.34 ‡,‖ | 66 ‡,‖ | 90 | 1000 | 320,45 ± 0.62 |
| 50 | 15 *,†,§ | 1.16 ± 0.64 *,†,§,┴ | 0.66 ± 0.21 *,†,§,┴ | 1.47 §,┴ | 71 §,┴ | 93 | 300.31 ± 0.52 | |||
| 3DPQ-4 | 5 | 1.88 ‡,‖ | 10 *,† | 2.39 ± 0.56 *,†,‡,‖ | 0.98 ± 0.31 *,†,‡,‖ | 1.23 ‡,‖ | 64 ‡,‖ | 90 | 1000 | 320.73 ± 0.36 |
| 50 | 14 *,† | 1.33 ± 0.15 *,†,§,┴ | 0.41 ± 0.23 *,†,§,┴ | 1.51 §,┴ | 76 §,┴ | 93 | 305.56 ± 0.68 | |||
| 3DPQ-9 | 5 | 2.02 ‡,‖ | 12 *,†,‡ | 2.28 ± 0.47 *,†,‡,‖ | 0.77 ± 0.32 *,†,‡,‖ | 1.28 ‡,‖ | 62 ‡,‖ | 94 ‡ | 1000 | 315.54 ± 0.65 |
| 50 | 15 *,†,§ | 1.14 ± 0.65 *,†,§,┴ | 0.40 ± 0.43 *,†,§,┴ | 1.31 §,┴ | 78 §,┴ | 97 | 310.33 ± 0.95 | |||
| 3DPQ-12 | 5 | 2.06 ‡,‖ | 12 *,†,‡ | 2.24 ± 0.54 *,†,‡,‖ | 0.67 ± 0.22 *,†,‡,‖ | 1.24 ‡,‖ | 63 ‡,‖ | 93 ‡ | 1000 | 305.06 ± 0.94 |
| 50 | 15 *,†,§ | 0.94 ± 0.35 *,†,§,┴ | 0.34 ± 0.11 *,†,§,┴ | 1.31 §,┴ | 71 §,┴ | 96 | 299.56 ± 0.45 | |||
| 4-OTH. j | 5 | 3.64 ‖ | 7 * | 3.36 ± 0.38 *,†,‖ | 1.88 ± 0.35 *,†,‖ | 1.85 | 35 | 88 ‖ | 1000 | 305.84 ± 0.59 |
| 50 | 10 *,† | 3.22 ± 0.21 *,†,┴ | 1.35 ± 0.63 *,†,┴ | 2.52 ┴ | 42 | 94 | 297.65 ± 0.39 | |||
| Ral. k | 5 | 2.39 ‡ | 8 * | 3.11 ± 0.47 *,†,‡ | 1.67 ± 0.31 *,†,‡ | 1.85 | 36 | 93 ‡ | 1000 | 310.54 ± 0.45 |
| 50 | 13 *,† | 2.91 ± 0.22 *,†,§ | 1.41 ± 0.54 *,†§ | 1.90 § | 42 | 96 | 300.54 ± 0.48 | |||
| MNU l | 50 | NA o | 5 *,†,‡,§,‖,┴ | 4.55 ± 0.15 *,‡,§,‖,┴ | 4.48 ± 0.54 | NA | NA | NA | 100 | 305.44 ± 0.62 |
| C m | NA | 0 †,‡,§,‖,┴ | 0 †,‡,§,‖,┴ | 0 †,‡,§,‖,┴ | NA | NA | NA | NA | 210.54 ± 0.29 | |
| Placebo n | NA | NA | NA | NA | NA | NA | NA | NA | 300.54 ± 0.63 | |
| NA | NA | NA | NA | NA | NA | NA | NA | 325.43 ± 0.29 |
a The average lipophilicity form the concentration range 5, 10, 20, 30, 40, and 50 mg/kg of bwt measured using shake-flask methodology; b Plasma protein binding (PPB) at 37 °C; c Intrinsic clearance in vivo; d Bioavailability of compound; e Maximum-tolerated-dose obtained after the 5-days per os administration in the concentration of 5, 50, 100, 500, and 1000 mg/kg bwt; f The effect of the orally administered compound at maximum-tolerated-dose; g The effect of the orally administered compound at maximum-feasible-dose on the body weight at day 1, showing the average body weight (mg) in placebo/control and the compound-treated rats; h The effect of the orally administered compound at maximum-feasible-dose on the bodyweight 5 days after starting treatment at the time of sacrifice, showing the average body weight (mg) in placebo/control and the compound-treated rats; i Results are presented as mean value ± standard deviation; j 4-hydroxytamoxifen; k Raloxifene; l Methyl nitrosourea; m 0.9% NaCl; n Vehicle; carboxymethylcellulose; o Not available. * p < 0.05 when compared with control group; † p < 0.05 when compared with MNU in concentration of 50 mg/kg; ‡ p < 0.05 when compared with 4-OTH in concentration of 5 mg/kg; § p < 0.05 when compared with 4-OTH in concentration of 50 mg/kg; ‖ p < 0.05 when compared with Ral in concentration of 5 mg/kg; ┴ p < 0.05 when compared with Ral in concentration of 50 mg/kg.