Kukoamine A analogs with lipoxygenase inhibitory activity

Figures & data

Figure 1.  Structures of compounds encountered in the present work.

Table 1.  Interaction percent with DPPH (RA %), in vitro inhibition of soybean lipoxygenase (LOX) (IC₅₀), inhibition percent of lipid peroxidation (AAPH %), and inhibition percent of carrageenan-induced rat paw edema (ICPE %) by KukA and analogs.

Compounds	Clog P	RA %, 0.1 mM 20/60 min	IC50 μM or % inhibition, 0.1 mM LOX	AAPH %, 0.1 mM	ICPE %, 0.01 mmol/kg
CA	0.82	5.5	600 μM (IC50)	17.5
DHCA	0.45	100	16%	47
SPM	−2.33	4	NA	NA
SPD	−1.48	NA	NA	NA
DHCA + SPM (2:1)		12	5.4%	72.4
DHCA + SPD (2:1)		7	30%	88.5
KukA	−1.79	96	9.5 μM (IC50)	72	43*
KukB	−1.66	97.5	22%	22
KukC	−1.53	NA	30%	18
KukD	−1.13	42.5	32%	11
1	−2.83	97	16%	36
2	0.57	5	5.4%	68
3	1.42	52	62 μM (IC50)	100	42*
4	2.35	51	72 μM (IC50)	92
5	2.51	61	20%	100
6	1.99	57	17%	36
7	1.42	10	41%	93
NDGA		81	84%
Trolox				63
Indomethacin					47**

Note. The effect on edema is expressed as percent of weight increase of hind paw (and as percent of inhibition of edema) in comparison to controls. Each value represents the mean obtained from 6–15 animals in two independent experiments. In all cases, significant difference from control: *p < 0.1, **p < 0.01 (Student’s t test); NA, no activity.