Table 1.

Inhibition of mitoxantrone efflux in ABCG2-transfected cells, and cytotoxicity

Indenoindoles	ABCG2 inhibition		Cytotoxicity	TRe
	% at 10 µMa	IC50 (µM)	IG50 (µM)d
Ketonic reference
4c	100±14	0.43±0.01b	30.7±9.5	71
Phenolic derivatives
5a	45	∼12c	>10	≥1
5b	68	∼7c	>4	≥1
5c	81±5	0.16±0.02b	42.7±9.7	267
5d	98±25	0.64±0.23b	>100	>156
5e	56	∼9c	4.8±0.9	<1
5f	92±22	0.16±0.01b	42.3±2.8	264
5g	111±2	0.51±0.09b	>100	>196
5h	85±11	0.15±0.01b	54±14	360
5i	100±10	0.37±0.09b	45.7±6.1	124
5j	111±14	0.20±0.01b	0.8±0.1	4
p-Quinonic derivatives
6a	36	∼14c	1.3±0.4	<1
6b	10	∼50c	0.53±0.15	<1
6c	18	∼30c	6.9±2.1	<1
6d	33	∼15c	6.8±0.5	<1
6e	41	∼13c	7.1±1.1	<1
6f	99±9	0.84±0.31b	15.6±5.9	19
6g	128±6	0.43±0.01b	3.7±2.2	9

Notes:

^aThe percentage inhibition of ABCG2-mediated mitoxantrone efflux was determined for each compound at a fixed concentration of 10 μM.

^bFor the best compounds producing at least 50% inhibition at 10 μM, a concentration range was analyzed in order to precisely determine the IC₅₀ values; the data show mean±SD.

^cFor the other, less potent compounds, a rough estimation was obtained from the experimental inhibition produced at 10 μM.

^dThe IG₅₀ values of compounds cytotoxicity were determined after 72 hours of treatment with the MTT cell-survival method.

^eThe TR was calculated by dividing the IG₅₀ values of cytotoxicity with the corresponding IC₅₀ values of ABCG2 inhibition.

Abbreviations: IC₅₀, half-maximal inhibitory concentration; IG₅₀, half-maximal inhibitory growth concentration; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TR, therapeutic ratio.