TABLE 1.

Binding affinity (K_d) of compounds 1a-o and their inhibitory effect on LPS-induced NF-κB/AP-1 transcriptional activity in THP-1Blue cells and IL-6 production in MonoMac-6 cells.

Compd.	XR	Binding affinity			THP-1Blue NF-κB/AP-1	MonoMac-6 IL-6 production
		JNK1	JNK2	JNK3
			Kd (μM)			IC50 (μM)
TRYP-Ox a	-OH	0.15 ± 0.081 a	1.0 ± 0.14 a	0.275 ± 0.21 a	3.8 ± 1.1 a	3.2 ± 1.2 a
1a	-OCH3	3.1 ± 0.8	5.6 ± 0.4	1.4 ± 0.2	20.8 ± 5.3	23.5 ± 1.8
1b	-OC2H5	3.2 ± 1.2	5.4 ± 0.6	1.2 ± 0.4	N.A.	N.A.
1c	-OCH2CH=CH2	3.6 ± 0.7	4.1 ± 0.1	0.85 ± 0.01	18.9 ± 1.8	N.A.
1d	-OC(CH3)3	9.3 ± 0.5	12.0 ± 1.4	2.3 ± 0.3	N.A.	N.A.
1e	OCH2CN	19.5 ± 3.5	17.5 ± 2.1	1.5 ± 0.6	N.A.	N.A.
1f		n.d.	n.d.	N.B.	N.A.	N.A.
1g		n.d.	n.d.	N.B.	N.A.	N.A.
1h		Poor solubility b			N.A.	N.A.
1i		4.0 ± 0.9	3.9 ± 0.4	1.5 ± 0.1	N.A.	N.A.
1j		0.34 ± 0.04	0.49 ± 0.01	0.18 ± 0.04	0.8 ± 0.2	1.7 ± 0.1
1k	-OLi	0.47 ± 0.03	0.62 ± 0.035	0.17 ± 0.03	0.9 ± 0.1	1.1 ± 0.2
1l	-ONa	0.44 ± 0.07	0.58 ± 0.014	0.22 ± 0.04	0.9 ± 0.2	1.8 ± 0.2
1m	-NH2	Poor solubility b			N.A.	N.A.
1n	-NHPh	Poor solubility b			N.A.	N.A.
1o		0.47 ± 0.03	0.62 ± 0.035	0.17 ± 0.03	3.3 ± 0.1	6.6 ± 1.2

^aData for from (Schepetkin et al., 2019).

^bCompound was insufficiently soluble in dimethyl sulfoxide (DMSO) for the binding affinity assay.

N.A., no inhibition at concentrations ≤ 50 μM; n.d., not determined; N.B., no JNK binding at concentrations ≤ 30 μM.