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. Author manuscript; available in PMC: 2008 Jan 1.
Published in final edited form as: Bioorg Med Chem. 2006 Oct 10;15(1):495–510. doi: 10.1016/j.bmc.2006.09.039

Table 2.

Structures of Quninoline-5,8-diones and Their In Vitro Differential Cytotoxicity

graphic file with name nihms14804t2.jpg
LC50 (μM)a
Cell Linesb
No. R1 R2 R3 R4 NRK K/1 H/1.2 N/4.2 3LL
3 CH3COHN H H CHO 1.3 2.6 2.5 NT 1.2
4 ClCH2CONH H H CHO 3.6 5.8 3.4 3.2 2.1
5 n-C3H7COHN H H CHO 3.0 >3.3 3.3 >3.3 2.5
6 i-C3H7COHN H H CHO >3.3 2.15 >3.3 >3.3 1.0
47 CH3COHN H H CH3a 2.4 5.9 4.4 NT 2.0
48 ClCH2CONH H H CH3 3.2 6.6 2.8 3.4 2.3
49 n-C3H7COHN H H CH3 2.0 >3.3 >3.3 >3.3 2.5
50 i-C3H7COHN H H CH3 1.5 7.5 1.45 1.15 0.71
51 CH3CONH H CH3 H 1.3 1.8 1.1 NT 1.0
52 H CH3COHN H CH3 21.5 >33 20 NT >33
53 CH3CONH H H COOH >33 >33 >31 NT 26
54 H2N H H CH3 0.8 1.3 0.6 NT 0.8
55 H2N H H CHO 2.4 4.3 2.2 NT 2.3
56 CH3O H H CH3 6.9 11.8 4.2 NT 7.4
57 HO(CH2)4NH H H CH3 10.5 13.5 10.5 NT 3.8
a

LC50 is the concentration of analogue that afforded 50% reduction in colony number after a 5-day incubation. Most of the reported values are derived from representative experiments performed in triplicate and interpolated from at least eight different concentrations of drugs ranging from 0.01 to 33 μM. Those values reported as > 3.3 were determined in screening assays where only two concentrations of drug were used, i.e. 3.3 and 33 μM. All experiments were performed at least twice and the data presented for each compound is that obtained from one experiment. See Experimental Section for culture details. NT = Not tested.

b

Cell lines: NRK, normal rat kidney epithelial; K/1, K-ras transformed normal rat kidney epithelial; H/1.2, H-ras transformed normal rat kidney epithelial; N/4.2, N-ras transformed normal rat kidney epithelial; and 3LL, Lewis Lung carcinoma.

For the syntheses of quinolinediones 3, 42 see references 36, 37; for 5, 49 see reference 40; for 4 and 49 see reference 42 and for 50, 54, 56 see reference 48.