Bioactivities detected with the quinazolinone C derivatives The compounds were evaluated for their binding abilities to FPRL1 in competition with [125I]WKYMVm. Agonist activities were assessed in HeLa cells stably transfected with human FPRL1 gene and a pNF-κB-Luc reporter plasmid. Calcium responses were examined in RBL-2H3 cells stably transfected with human FPRL1 genes (RBL-FPRL1). Efficacy was expressed as a percentage of the maximal response that elicited by 10 μM (in the reporter assay) or 1 μM (in the calcium mobilization assay) WKYMVm. Each value represents means ± S.E.M. of three independent experiments.
Compound | FPRL1 Binding, IC50 | Reporter Assay | Calcium Mobilization | ||||
|---|---|---|---|---|---|---|---|
| EC50 | Efficacy | EC50 | Efficacy | ||||
| nM | nM | % | μM | % | |||
| Hit (C8) | 745 ± 104 | 472 ± 9 | 54.3 ± 0.1 | 12.34 ± 0.83 | 43 ± 3 | ||
| C1 | 92 ± 1 | 15 ± 4 | 88.5 ± 9.1 | 0.47 ± 0.02 | 90 ± 4 | ||
| C5 | 174 ± 61 | 46 ± 10 | 87.6 ± 5.0 | 1.48 ± 0.15 | 74 ± 4 | ||
| C7 | 6653 ± 859 | N.A. | N.A. | N.A. | N.A. | ||
| C9 | >15,000 | 8064 ± 487 | 52.7 ± 4.2 | N.A. | N.A. | ||
| C10 | 261 ± 59 | 89 ± 8 | 86.7 ± 11.5 | 1.10 ± 0.17 | 55 ± 3 | ||
| C11 | >15,000 | 1352 ± 201 | 31.1 ± 3.9 | N.A. | N.A. | ||
| C12 | >15,000 | N.A. | N.A. | N.A. | N.A. | ||
| WKYMVm | 0.4 ± 0.1 | 1.3 ± 0.2 | 100 | 0.0011 ± 0.0001 | 100 | ||
N.A., no activity (efficacy <15%, or potency >20 μM)