Table 3.
Activity of 9a-h, 10 in human neutrophils and FPR-transfected HL60 cells
| ||||||
|---|---|---|---|---|---|---|
| Compd | R4 | R5 | Ca2+ flux | |||
| human neutrophils | FPR1-HL60 | FPR2-HL60 | FPR3-HL60 | |||
| EC50 (μM) and efficacy (%)[a] | ||||||
| 9a | CH3 | COCH3 | 12.2 ± 2.5(55) | 8.9 ± 1.9 (75) | 5.8 ± 1.4 (60) | N.A.[b] |
| 9b | CH3 | H | 10.7 ± 2.3 (55) | 12.4 ± 2.6 (70) | 4.1 ± 1.1 (80) | 27.8 ± 3.2 (85) |
| 9c | Ph | H | 6.0 ± 1.5 (95) | 1.8 ± 0.6 (100) | 2.1 ± 0.6 (95) | 19.7 ± 2.4 (135) |
| 9d | 3-OCH3Ph | H | 1.3 ± 0.3 (125) | 0.28 ± 0.08 (90) | 0.23 ± 0.04 (120) | 5.1 ± 1.7 (100) |
| 9e | 4-OCH3Ph | H | 7.4 ± 2.3 (110) | 2.6 ± 0.6 (110) | 1.8 ± 0.16 (100) | 36.1 ± 3.3 (85) |
| 9f | 3-ClPh | H | 11.1 ± 2.8 (140) | 6.0 ± 1.7 (75) | 3.0 ± 0.7 (110) | 32.2 ± 3.6 (75) |
| 9g | 4-ClPh | H | 12.2 ± 3.1 (125) | 2.8 ± 0.7 (75) | 2.4 ± 0.5 (75) | N.A. |
| 9h | 4-NO2Ph | H | 1.5 ± 0.4 (95) | 9.1 ± 1.4 (60) | N.A. | N.A. |
| 10 | 4-NH2Ph | H | 36.1 ± 3.9 (65) | 34.9 ± 4.2 (80) | 14.7 ± 3.7 (65) | N.A. |
[a]
EC50 values represent the average of means from three independent experiments and were determined by nonlinear regression analysis of the concentration-response curves (5-6 points) generated using GraphPad Prism 5 with 95% confidential interval (p < 0.05). Efficacy is expressed as % of the response induced by 5 nM fMLF (FPR1-HL60), 5 nM WKYMVm (FPR2-HL60), or 10 nM WKYMVM (FPR3-HL60).
[b]
N.A., no activity (no response was observed during first 2 min after addition of compounds under investigation) considering the limits of efficacy > 20% and EC50 < 50 μM.