Table 1.

Inhibition of hNQO1 by indolequinones 1 and 5–29, and inhibition of cell growth in the MIA PaCa-2 cell line

No.	R3	R5	R6	X	Mechanism-based inhibitiona	Partition ratiob	>90% Inhibition of NQO1 in MIA PaCa-2 cellsb/nM	IC50 MIA PaCa-2 4 h/nMc	IC50 MIA PaCa-2 72 h/nMc
1	H	OMe	H	OAr Ar=4-NO2-C6H4	yes	3.5	10–100	629±17	508±5
15	H	H	Ome	OAr Ar=4-NO2-C6H4	yes	3.7	10–100	638±15	355±3
5	H	OMe	H	OAr Ar=C6H5	yes	4000	nd	1385±24	962±18
16	H	H	Ome	OAr Ar=C6H5	yes	3800	nd	4563±26	409±30
17	H	H	OMe	OAr Ar =4-NH2-C6H4	no	nd	nd	504±4	160±4
6	H	OMe	H	OAr Ar=3-NO2-C6H4	yes	2.3	10–100	352±16	258±21
18	H	H	OMe	OAr Ar=3-NO2-C6H4	yes	3.5	10–100	351±25	257±22
7	H	OMe	H	OAr Ar=2-NO2-C6H4	yes	1.0	nd	345±20	104±18
19	H	H	OMe	OAr Ar=2-NO2-C6H4	yes	1.0	10–100	363±9	178±4
8	H	OMe	H	OAr Ar=2,4-(NO2)2-C6H3	see text	nd	nd	NC	NC
20	H	H	OMe	OAr Ar=2,4-(NO2)2-C6H3	see text	nd	nd	NC	NC
9*	H	OMe	H	OAr Ar=2-F-4-NO2-C6H3	yes	0.8	nd	4654±48	3556±31
21	H	H	OMe	OAr Ar=2-F-4-NO2-C6H3	yes	0.8	10–100	529±5	417±5
22	H	H	OMe	OAr Ar=4-CN-C6H4	yes	37	nd	463±6	192±3
23	H	H	OMe	OAr Ar=4-CF3-C6H4	yes	652	5000–10000	496±3	311±5
24	H	H	OMe	OAr Ar=4-F-C6H4	yes	>100000	5000–10000	905±25	493±32
25	H	H	OMe	OAr Ar=2,4-F2-C6H4	yes	21.3	10–100	255±5	75±4
10	H	OMe	H	OAr Ar=2,4,6-F3-C6H4	yes	1.9	nd	427±5	86±3
26	H	H	OMe	OAr Ar=2,4,6-F3-C6H4	yes	1.7	10–100	452±4	212±3
11	H	OMe	H	OAr Ar=2-pyridyl	yes	nd	<10	NC	NC
27	H	H	OMe	OAr Ar=2-pyridyl	yes	1.1	10–100	9579±48	2393±28
12	H	OMe	H	OAr Ar=3-pyridyl	yes	6.1	10–100	904±26	562±24
28	H	H	OMe	OAr Ar=3-pyridyl	yes	nd	nd	2475±40	1824±19
13	H	OMe	H	OAr Ar=4-pyridyl	yes	1.3	nd	2007±16	2172±25
29	H	H	OMe	OAr Ar=4-pyridyl	yes	0.9	10–100	2560±7	3271±15
14	Me	OMe	H	OAr Ar=4-NO2-C6H4	yes	9.1	nd	1829±14	1696±23

^aclassification of mechanism-based inhibition refers to dependence (or not) on NADH;

^bnd not determined;

^cNC denotes no convergence. IC₅₀ value cannot be determined as profile is a straight line.

^*Compound 9 was found to be unstable in DMSO and was tested immediately for NQO1 mechansim-based inhibition.