Synthetic genistein derivatives as modulators of glycosaminoglycan storage

Table 2 Cytotoxic and antiproliferative activities of genistein synthetic derivatives and their effects on kinetics of GAG synthesis in fibroblasts

Compound	Cytotoxicity LC₅₀[μM]	Proliferation IC₅₀[μM]	GAG synthesis [%]
IFG-001	13.9	-	120 ± 56
IFG-018	41.7	-	76 ± 38
IFG-021	11.0	-	75 ± 25
IFG-027	13.1	-	69 ± 46
IFG-032	n/c	17.4	57 ± 24
IFG-034	n/c	22.9	65 ± 19
IFG-035	22.6	-	93 ± 70
IFG-036	n/c	11.2	64 ± 21
IFG-037	23.5	-	88 ± 84
IFG-038	n/c	19.9	55 ± 13
IFG-042	22.0	-	48 ± 29
IFG-043	14.5	-	46 ± 41
IFG-046	20.7	-	118 ± 72
IFG-048	20.3	-	73 ± 5
IFG-050	11.6	-	100 ± 65
IFG-051	14.6	-	127 ± 109
IFG-052	15.8	-	74 ± 19
IFG-053	n/c	53.0	92 ± 52
IFG-054	n/c	n/a	119 ± 64
IFG-060	14.9	-	31 ± 8
IFG-061	18.8	-	50 ± 25
IFG-062	12.1	-	403 ± 206
IFG-063	51.5	-	76 ± 6
IFG-064	6.6	-	133 ± 77
IFG-065	22.7	-	96 ± 22
IFG-066	n/c	14.6	34 ± 10
IFG-067	15.1	-	96 ± 38
IFG-070	n/c	48.1	101 ± 30
IFG-071	n/c	17.9	49 ± 20
IFG-072	n/c	14.1	79 ± 42
IFG-073	27.5	-	83 ± 32
IFG-074	44.1	-	88 ± 39
Genistein	n/c	16.9	55 ± 31

Cytotoxicity is expressed as LC₅₀ index value, i.e. concentration of the tested drug [μM] that is lethal to 50% of cells in a culture exposed to the tested compound for 24 hours. Antiproliferative activity is expressed as IC₅₀ index value, i.e. concentration of the tested drug [μM] that causes 50% inhibition of cell proliferation in a culture exposed to the tested compound for 7 days. Kinetics of GAG synthesis is expressed as relative ³⁵ S incorporation into GAGs after 3-day exposure to derivatives of genistein at 30 μM concentration. Labeling was conducted for 24 hours with 20 μCi/ml H₂[³⁵ S]O₄. Radioactivity of incorporated ³⁵ S was measured in a scintillation counter, calculated per DNA amount [dpm/ng DNA] and expressed as the percentage of control, where 100% corresponds to the relative ³⁵ S incorporation into control (cell culture treated with 0.05% dimethylformamide).
n/c denotes experiments in which no cytotoxicity was observed (over 90% of cells survived at concentrations ranging from 1 to 30 μM).
n/a denotes experiments in which no antiproliferative activity was observed (relative proliferation was over 95% at concentrations ranging from 1 to 30 μM).
- denotes experiments in which IC₅₀ for antiproliferative activities could not be determined due to cytotoxic effects of the tested compounds.

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