QSAR of aromatic substances: MAO inhibitory activity of xanthone derivatives

Figures & data

Figure 1 Numbering of xanthones skeleton used in the HyperChem and NODANGLE calculations. (compound 1 in Table I).

Figure 2 Numbering of the xanthones skeleton and angles used in the interpretations. Angles shown are for compound 1.

Table I.  MAO Inhibitory activities of xanthone derivatives.

No.	R1	R2	R3	R4	R5	R6	R7	R8	IC50 MAO-A (μM)
1	H	H	H	H	H	H	H	H	0.84 ± 0.08
2	OH	H	H	H	H	H	H	H	0.31 ± 0.05
3	MeO	H	H	H	H	H	H	H	0.9 ± 0.1
4	H	OH	H	H	H	H	H	H	3.8 ± 0.3
5	H	MeO	H	H	H	H	H	H	5.3 ± 0.4
6	H	H	OH	H	H	H	H	H	1.1 ± 0.3
7	H	H	MeO	H	H	H	H	H	0.18 ± 0.03
8	H	H	H	OH	H	H	H	H	1.3 ± 0.1
9	H	H	H	MeO	H	H	H	H	30 ± 3.2
10	OH	H	H	H	OH	H	H	H	0.73 ± 0.1
11	H	H	OH	H	OH	H	H	H	4.5 ± 0.2
12	H	H	OH	H	MeO	H	H	H	23 ± 1.4
13	OH	H	MeO	H	H	H	H	H	0.11 ± 0.01
14	MeO	H	MeO	H	H	H	H	H	20.2 ± 0.48
15	H	H	MeO	H	MeO	H	H	H	36 ± 2.9
16	MeO	H	H	H	OH	H	H	H	51 ± 7.8
17	H	H	MeO	OH	H	H	H	H	18 ± 3.1
18	H	H	OH	MeO	H	H	H	H	65 ± 6.8
19	H	H	MeO	MeO	H	H	H	H	31 ± 4.8
20	OH	H	OH	H	OH	H	H	H	3.8 ± 0.25
21	OH	H	MeO	H	OH	H	H	H	0.04 ± 0.005
22	OH	H	MeO	H	MeO	H	H	H	29 ± 4.3
23	MeO	H	MeO	H	MeO	H	H	H	58 ± 6.8
24	OH	H	OH	Me	H	H	H	H	4.3 ± 0.4
25	OH	Me	OH	H	H	H	H	H	3.7 ± 0.2
26	OH	Me	OH	Cl	H	H	H	H	27 ± 1.1
27	OH	Me	OH	Br	H	H	H	H	14.9 ± 0.6
28^a	OH	H	OH	C10H17	OH	H	H	H	37 ± 5.5
29^b	OH	C5H9	H	OH	OH	H	H	H	3.3 ± 0.2
30^c	OH	H	C5H9	OH	OH	H	H	H	40 ± 3.7
31	OH	MeO	OH	H	OH	H	H	H	2.7 ± 0.4
32	OH	MeO	OH	H	MeO	H	H	H	51 ± 11
33	MeO	MeO	MeO	H	MeO	H	H	H	37 ± 2.0
34	OH	H	OH	H	H	H	OH	H	8 ± 1.2
35	OH	H	OH	H	OH	H	H	OH	13 ± 1.4
36	OH	H	MeO	H	OH	H	H	OH	0.66 ± 0.06
37	OH	H	OH	H	H	H	OH	OH	24 ± 4.6
38	OH	H	MeO	H	H	H	OH	OH	8.5 ± 0.8
39	OH	H	MeO	H	H	H	MeO	MeO	19 ± 1.0
40	OH	H	OH	H	H	OH	OH	H	25 ± 3.4
41	MeO	H	H	Me	OH	H	MeO	H	24 ± 7.0
42	OH	MeO	OH	H	MeO	OH	H	H	32 ± 5.0

Reprinted from Bioorg. Med. Chem. Lett. 14, M.B. Núñez, F.P. Maguna, N.B. Okulik and E.A. Castro, “QSAR Modelling of MAO inhibitory activity of xanthones derivatives”, 5611-5617, Copyright (2004), with permission from Elsevier

^a C₁₀H₁₇ is Me₂C = CH–CH₂–CH₂–C(Me) = CH–CH₂

^b C₅H₉ is CH₂ = CH–CMe₂

^c C₅H₉ is Me₂ = CH–CH₂.

Table II.  Orbital energies (eV) and angles (°) of the compounds in Table 1.

Compound	HOP1	SHOP1	LUP1	SLUP1	Φ1H	Φ1L	HOP3	SHOP3	LUP3	Compound	SLUP3	Φ3H	Φ3L	HOP2	SHOP2	LUP2	SLUP2	Φ2H	Φ2L	IC50(obs)
1	− 9.191	− 10.109	− 0.709	− 0.249	39.5	20.3	− 9.191	− 10.109	− 0.709	1	− 0.249	39.5	20.3	− 10.109	− 10.166	− 0.249	1.520	0.0	30.0	0.84
2	− 9.074	− 9.796	− 0.841	− 0.353	35.2	20.5	− 9.074	− 9.796	− 0.841	2	− 0.353	62.8	17.9	− 10.241	–	− 0.353	1.352	4.0	30.2	0.31
3	− 9.021	− 9.553	− 0.551	− 0.194	34.4	22.4	− 9.021	− 9.553	− 0.551	3	− 0.194	61.5	16.4	− 10.053	− 10.151	− 0.194	1.663	15.0	30.2	0.9
4	− 8.958	− 9.919	− 0.802	− 0.280	42.0	20.4	− 8.958	− 9.919	− 0.802	4	− 0.280	34.3	21.8	− 9.919	− 13.536	− 0.280	1.451	7.0	30.7	3.8
5	− 9.842	− 10.132	− 0.732	− 0.219	34.0	20.2	− 8.853	− 9.842	− 0.732	5	− 0.219	38.3	21.1	− 9.842	− 10.132	− 0.219	1.509	11.0	31.0	5.3
6	− 9.250	− 9.681	− 0.712	− 0.286	42.0	19.5	− 9.250	− 9.681	− 0.712	6	− 0.286	18.0	21.9	− 9.681	− 10.299	− 0.286	1.478	− 5.0	28.9	1.1
7	− 9.176	− 9.579	− 0.654	− 0.232	43.0	19.8	− 9.176	− 9.579	− 0.654	7	− 0.232	16.0	21.2	− 9.579	− 10.231	− 0.232	1.536	− 3.0	29.1	0.18
8	− 9.073	− 9.807	− 0.812	− 0.354	36.5	20.7	− 9.073	− 9.807	− 0.812	8	− 0.354	66.6	17.0	− 10.255	–	− 0.354	1.430	7.0	30.6	1.3
9	− 8.882	− 9.704	− 0.685	− 0.236	38.4	22.3	− 8.882	− 9.704	− 0.685	9	− 0.236	60.9	17.3	− 10.095	–	− 0.236	1.539	11.0	30.9	30
10	− 9.067	− 9.577	− 0.942	− 0.455	62.0	17.3	− 9.067	− 9.577	− 0.942	10	− 0.455	57.7	18.2	− 10.390	− 13.028	− 0.455	1.265	− 5.0	29.6	0.73
11	− 9.129	− 9.910	− 0.813	− 0.388	69.0	16.2	− 9.129	− 9.728	− 0.813	11	− 0.388	21.3	22.4	− 10.424	− 13.045	− 0.388	1.389	11.0	28.2	4.5
12	− 8.946	− 9.817	− 0.691	− 0.266	63.0	16.5	− 8.946	− 9.565	− 0.691	12	− 0.266	24.7	24.2	− 10.288	− 12.414	− 0.266	1.499	13.0	28.1	23
13	− 9.131	− 10.016	− 0.770	− 0.316	33.3	20.0	− 9.131	− 9.507	− 0.770	13	− 0.316	72.1	18.9	− 10.016	− 11.614	− 0.316	1.383	8.0	29.4	0.11
14	− 9.088	− 9.874	− 0.490	− 0.171	35.2	21.4	− 9.088	− 9.317	− 0.490	14	− 0.171	54.2	17.4	− 9.874	− 11.399	− 0.171	1.675	6.0	29.3	20.2
15	− 8.893	− 9.764	− 0.636	− 0.214	62.0	16.6	− 8.893	− 9.455	− 0.636	15	− 0.214	23.2	23.7	− 10.228	–	− 0.214	1.554	14.0	28.1	36
16	− 8.972	− 9.442	− 0.648	− 0.298	64.0	18.5	− 8.972	− 9.442	− 0.648	16	− 0.298	53.2	17.0	− 10.253	–	− 0.298	1.573	− 3.0	29.7	51
17	− 9.372	− 10.149	− 0.749	− 0.332	47.0	20.3	− 8.940	− 9.372	− 0.749	17	− 0.332	95.4	18.1	− 10.149	− 11.995	− 0.332	1.455	5.0	29.6	18
18	− 9.244	− 10.199	− 0.750	− 0.367	38.0	19.9	− 9.244	− 9.503	− 0.750	18	− 0.367	56.5	21.7	− 10.199	–	− 0.367	1.390	8.0	27.8	65
19	− 9.176	− 10.139	− 0.698	− 0.294	37.1	19.5	− 9.176	− 9.385	− 0.698	19	− 0.294	62.8	22.6	− 10.139	–	− 0.294	1.475	5.0	28.0	31
20	− 9.156	− 9.573	− 0.923	− 0.488	65.0	17.1	− 9.156	− 9.573	− 0.923	20	− 0.488	56.6	18.4	− 10.273	− 11.989	− 0.488	1.236	17.0	28.7	3.8
21	− 9.095	− 9.478	− 0.867	− 0.414	64.0	16.7	− 9.095	− 9.478	− 0.867	21	− 0.414	59.4	19.3	− 11.717	–	− 0.414	1.298	− 23.2	28.6	0.04
22	− 8.900	− 9.704	− 0.749	− 0.300	58.0	17.0	− 8.900	− 9.341	− 0.749	22	− 0.300	62.0	21.4	− 11.560	–	− 0.300	1.403	− 22.0	28.1	29
23	− 8.821	− 9.533	− 0.471	− 0.157	60.0	17.3	− 8.821	− 9.236	− 0.471	23	− 0.157	44.0	20.8	− 9.958	− 11.345	− 0.157	1.692	18.0	28.0	58
24	− 10.018	− 10.314	− 0.816	− 0.354	35.2	19.7	− 9.068	− 9.516	− 0.816	24	− 0.354	71.5	19.5	− 10.018	− 11.695	− 0.354	1.326	9.0	29.1	4.3
25	− 9.921	− 10.282	− 0.800	− 0.378	38.8	20.5	− 9.067	− 9.530	− 0.800	25	− 0.378	57.5	17.8	− 9.921	− 11.777	− 0.378	1.330	15.0	29.2	3.7
26	− 9.989	− 10.372	− 0.933	− 0.505	39.5	19.8	− 9.069	− 9.582	− 0.933	26	− 0.505	57.6	19.4	− 9.989	− 11.612	− 0.505	1.181	16.0	28.2	27
27	− 9.995	− 10.379	− 0.938	− 0.514	39.7	19.3	− 9.118	− 9.610	− 0.938	27	− 0.514	52.7	20.7	− 9.995	− 11.456	− 0.514	1.165	16.0	27.3	14.9
28	− 9.072	− 9.454	− 0.886	− 0.426	61.0	16.3	− 9.072	− 9.454	− 0.886	28	− 0.426	60.8	20.2	–	–	− 0.426	1.270	–	31.8	37
29	− 9.505	− 10.180	− 1.025	− 0.546	81.0	17.5	− 8.770	− 10.180	− 1.025	29	− 10.051	71.2	15.5	− 10.368	–	− 0.546	1.184	− 8.8	29.9	3.3
30	− 8.842	− 10.084	− 1.005	− 0.511	81.0	17.6	− 8.842	− 9.471	− 1.005	30	− 0.511	74.8	15.9	− 10.313	− 11.836	− 0.511	1.197	13.0	30.4	40
31	− 9.077	− 9.619	− 0.979	− 0.550	63.0	17.0	− 9.077	− 9.619	− 0.979	31	− 0.550	43.8	18.3	− 11.988	− 12.981	− 0.550	1.155	26.0	31.4	2.7
32	− 8.892	− 9.494	− 0.858	− 0.435	58.0	17.2	− 8.892	− 9.494	− 0.858	32	− 0.435	45.7	20.4	− 11.822	–	− 0.431	1.263	25.0	32.1	51
33	− 8.739	− 9.398	− 0.511	− 0.231	58.0	17.9	− 8.739	− 9.257	− 0.511	33	− 0.231	42.2	19.7	− 9.426	− 11.736	− 0.292	1.502	16.0	32.6	37
34	− 9.032	− 9.881	− 0.918	− 0.418	32.9	21.8	− 9.032	− 9.596	− 0.918	34	− 0.418	64.9	18.3	− 9.881	− 12.884	− 0.418	1.256	8.0	31.5	8
35	− 8.899	− 10.438	− 1.073	− 0.582	76.0	14.7	− 9.612	− 9.939	− 1.073	35	− 0.582	79.5	19.5	− 12.514	–	− 0.593	1.108	− 5.0	30.6	13
36	− 8.821	− 10.377	− 1.003	− 0.515	76.0	14.8	− 9.469	− 9.879	− 1.003	36	− 0.515	93.1	19.7	− 12.194	–	− 0.515	1.140	− 1.0	31.7	0.66
37	− 8.875	− 10.266	− 1.058	− 0.523	48.0	20.0	− 9.578	− 9.935	− 1.058	37	− 0.523	97.1	18.5	− 12.732	–	− 0.523	1.093	3.0	28.3	24
38	− 8.823	− 10.218	− 1.003	− 0.448	48.0	19.7	− 9.479	− 9.835	− 1.003	38	− 0.448	100.9	19.3	− 12.497	–	− 0.448	1.155	9.0	28.2	8.5
39	− 8.848	− 10.164	− 0.783	− 0.290	43.0	22.0	− 8.848	− 9.340	− 0.783	39	− 0.290	60.8	19.1	− 9.684	–	− 0.290	1.389	17.0	31.2	19
40	− 9.075	− 9.679	− 0.899	− 0.465	16.8	22.4	− 9.075	− 9.613	− 0.899	40	− 0.465	72.0	18.0	− 9.679	− 12.695	− 0.465	1.232	9.0	30.0	25
41	− 8.722	− 9.281	− 0.652	− 0.251	47.0	19.1	− 8.722	− 9.281	− 0.652	41	− 0.251	60.4	18.1	–	–	− 0.251	1.560	–	31.5	24
42	− 9.563	− 9.804	− 0.932	− 0.540	− 45.2	22.1	− 9.139	− 9.563	− 0.932	42	− 0.540	51.8	16.3	− 9.566	–	− 0.542	1.166	81.2	31.2	32

Energy of: HOP, Highest Occupied π Orbital; SHOP, Second Highest Occupied π Orbital; LUP, Lowest Unoccupied π Orbital; SLUP, Second Lowest Unoccupied π Orbital; H, HOP; L, LUP, IC₅₀(obs), MAO-A inhibitory activity; Φ angles (as in Figure 2).

Table III.  Calculated angles and their error terms.

Compound	Φ1H	α1H	Φ1L	α1L	Φ3H	α3H	Compound	Φ3L	α3L	Φ2H	α2H	Φ2L	α2L
1	39.5	0.0582	20.3	0.0813	39.5	0.0582	1	20.3	0.0813	0.0	0.1348	30.0	0.0102
2	35.2	0.0806	20.5	0.0909	62.8	0.0431	2	17.9	0.1359	4.0	0.0471	30.2	0.0078
3	34.4	0.0607	22.4	0.0716	61.5	0.0569	3	16.4	0.0756	15.0	0.3544	30.2	0.0167
4	42.0	0.0995	20.4	0.0943	34.3	0.0214	4	21.8	0.0704	7.0	0.1599	30.7	0.0047
5	34.0	0.0049	20.2	0.0904	38.3	0.0158	5	21.1	0.0564	11.0	0.2688	31.0	0.0040
6	42.0	0.0555	19.5	0.0737	18.0	0.0640	6	21.9	0.1063	− 5.0	0.2287	28.9	0.0235
7	43.0	0.0614	19.8	0.0704	16.0	0.0627	7	21.2	0.1164	− 3.0	0.2631	29.1	0.0216
8	36.5	0.0845	20.7	0.0812	66.6	0.0368	8	17.0	0.0806	7.0	0.0793	30.6	0.0065
9	38.4	0.0912	22.3	0.0960	60.9	0.0559	9	17.3	0.0656	11.0	0.2012	30.9	0.0076
10	62.0	0.0453	17.3	0.0899	57.7	0.0538	10	18.2	0.1374	− 5.0	0.0230	29.6	0.0051
11	69.0	0.0334	16.2	0.0727	21.3	0.0919	11	22.4	0.1065	11.0	0.3520	28.2	0.0177
12	63.0	0.0508	16.5	0.0581	24.7	0.1026	12	24.2	0.1226	13.0	0.3111	28.1	0.0171
13	33.3	0.0654	20.0	0.0826	72.1	0.0555	13	18.9	0.1798	8.0	0.2204	29.4	0.0158
14	35.2	0.0524	21.4	0.0599	54.2	0.0718	14	17.4	0.1109	6.0	0.1820	29.3	0.0233
15	62.0	0.0530	16.6	0.0555	23.2	0.0965	15	23.7	0.1353	14.0	0.3107	28.1	0.0185
16	64.0	0.0376	18.5	0.0720	53.2	0.0805	16	17.0	0.0763	− 3.0	0.0147	29.7	0.0123
17	47.0	0.0492	20.3	0.0750	95.4	0.0558	17	18.1	0.1070	5.0	0.1076	29.6	0.0160
18	38.0	0.0532	19.9	0.0814	56.5	0.0780	18	21.7	0.0965	8.0	0.1226	27.8	0.0410
19	37.1	0.0562	19.5	0.0781	62.8	0.0693	19	22.6	0.0998	5.0	0.1297	28.0	0.0377
20	65.0	0.0381	17.1	0.0850	56.6	0.0840	20	18.4	0.1733	17.0	0.2665	28.7	0.0127
21	64.0	0.0400	16.7	0.0814	59.4	0.0753	21	19.3	0.1822	− 23.2	0.3618	28.6	0.0119
22	58.0	0.0595	17.0	0.0673	62.0	0.0765	22	21.4	0.2031	− 22.0	0.3065	28.1	0.0134
23	60.0	0.0508	17.3	0.0454	44.0	0.1066	23	20.8	0.1345	18.0	0.2951	28.0	0.0183
24	35.2	0.0036	19.7	0.0791	71.5	0.0456	24	19.5	0.1806	9.0	0.2307	29.1	0.0208
25	38.8	0.0059	20.5	0.0851	57.5	0.0449	25	17.8	0.1759	15.0	0.3920	29.2	0.0190
26	39.5	0.0064	19.8	0.0932	57.6	0.0377	26	19.4	0.1536	16.0	0.4213	28.2	0.0318
27	39.7	0.0064	19.3	0.0915	52.7	0.0452	27	20.7	0.1592	16.0	0.4232	27.3	0.0445
28	61.0	0.0449	16.3	0.0760	60.8	0.0574	28	20.2	0.1883	–	–	31.8	0.0165
29	81.0	0.0222	17.5	0.0904	71.2	0.0107	29	15.5	0.1346	− 8.8	0.0295	29.9	0.0049
30	81.0	0.0219	17.6	0.0902	74.8	0.0167	30	15.9	0.1273	13.0	0.1670	30.4	0.0037
31	63.0	0.0462	17.0	0.0851	43.8	0.0507	31	18.3	0.1609	26.0	0.4333	31.4	0.0146
32	58.0	0.0684	17.2	0.0699	45.7	0.0533	32	20.4	0.1815	25.0	0.3638	32.1	0.0148
33	58.0	0.0604	17.9	0.0497	42.2	0.0627	33	19.7	0.1141	16.0	0.3099	32.6	0.0276
34	32.9	0.0206	21.8	0.0752	64.9	0.0866	34	18.3	0.1926	8.0	0.0917	31.5	0.0106
35	76.0	0.0147	14.7	0.1245	79.5	0.0615	35	19.5	0.1990	− 5.0	0.0589	30.6	0.0017
36	76.0	0.0146	14.8	0.1253	93.1	0.0591	36	19.7	0.2034	− 1.0	0.0073	31.7	0.0115
37	48.0	0.0185	20.0	0.1206	97.1	0.0590	37	18.5	0.2110	3.0	0.0315	28.3	0.0094
38	48.0	0.0180	19.7	0.1170	100.9	0.0647	38	19.3	0.2201	9.0	0.0898	28.2	0.0081
39	43.0	0.0132	22.0	0.0501	60.8	0.0865	39	19.1	0.1982	17.0	0.2939	31.2	0.0177
40	16.8	0.0391	22.4	0.1037	72.0	0.0746	40	18.0	0.1832	9.0	0.2655	30.0	0.0234
41	47.0	0.0223	19.1	0.0674	60.4	0.0828	41	18.1	0.0846	–	–	31.5	0.0103
42	− 45.2	0.0465	22.1	0.1082	51.8	− 9.5630	42	16.3	− 0.5400	81.2	0.3235	31.2	0.0409

H, HOP; α, error; Φ, angle (as in Figure 2).

Table IV.  Descriptors used in this study.

Name	Descriptor
HOP1	Energy of highest occupied π orbital for ring 1
SHOP1	Energy of second highest occupied π orbital for ring 1
LUP1	Energy of lowest unoccupied π orbital for ring 1
SLUP1	Energy of second lowest unoccupied π orbital for ring 1
HOP2	Energy of highest occupied π orbital for ring 2
SHOP2	Energy of second highest occupied π orbital for ring 2
LUP2	Energy of lowest unoccupied π orbital for ring 2
SLUP2	Energy of second lowest unoccupied π orbital for ring 2
HOP3	Energy of highest occupied π orbital for ring 3
SHOP3	Energy of second highest occupied π orbital for ring 3
LUP3	Energy of lowest unoccupied π orbital for ring 3
SLUP3	Energy of second lowest unoccupied π orbital for ring 3
S2Φ1H	Sin(2* the nodal angle in the highest occupied π orbital in ring 1)
C2Φ1H	Cos(2* the nodal angle in the highest occupied π orbital in ring 1)
S4Φ1L	Sin(4* the nodal angle in the lowest unoccupied π orbital in ring 1)
C4Φ1L	Cos(4* the nodal angle in the lowest unoccupied π orbital in ring 1)
S2Φ2H	Sin(2* the nodal angle in the highest occupied π orbital in ring 2)
C2Φ2H	Cos(2* the nodal angle in the highest occupied π orbital in ring 2)
S2Φ3H	Sin(2* the nodal angle in the highest occupied π orbital in ring 3)
S4Φ3L	Sin(4* the nodal angle in the lowest unoccupied π orbital in ring 3)
C2Φ3H	Cos(2* the nodal angle in the highest occupied π orbital in ring 3)
C4Φ3L	Cos(4* the nodal angle in the lowest unoccupied π orbital in ring 3)

Table V.  Progress of FLIPSTEP for the reduced model.

Variable	Coefficient	T	Significance	VIF
HOP1	1.0745	4.21	0.0002	2.38
SHOP1	− 1.2541	4.50	0.0001	2.31
SLUP1	− 0.1016	2.10	0.0447	1.52
HOP3	0.8591	1.85	0.0749	2.37
SHOP3	2.1089	5.12	0.0000	3.62
SLUP3	− 0.3177	0.38	0.7049	2.86
C2Φ1H	2.4483	5.95	0.0000	12.13
S2Φ1H	− 2.9982	7.18	0.0000	9.28
C2Φ3H	− 0.0525	0.22	0.8300	4.42
S2Φ3H	2.3561	7.36	0.0000	3.75
C4Φ1L	7.0778	5.68	0.0000	8.64
C4Φ3L	− 0.8675	1.18	0.2478	4.83

F = 13.59, R² = 0.8490, S = 0.3773

Table VI.  Flip status and flip significance for Equations (3) and (4).

	Equation (3) (all variables)		Equation (4) (all compounds)
Compound	Flip status	Flip significance	Flip Status	Flip Significance
1	− 1	0.9813	1	0.9917
2	1	0.8576	− 1	0.8265
3	1	0.0013	− 1	0.0007
4	1	0.9752	− 1	0.5680
5	− 1	0.0003	− 1	0.0000
6	− 1	0.0007	1	0.2435
7	− 1	0.0003	− 1	0.1014
8	− 1	0.1266	− 1	0.0153
9	− 1	0.0014	1	0.0359
10	1	0.3309	− 1	0.1572
11	1	0.4451	1	0.0124
12	1	0.1609	1	0.6900
13	1	0.0598	1	0.0303
14	− 1	0.0606	1	0.0426
15	− 1	0.9706	− 1	0.4480
16	1	0.0196	1	0.0007
17	− 1	0.1748	− 1	0.0100
18	− 1	0.0144	− 1	0.2926
19	− 1	0.0031	− 1	0.1022
20	1	0.3413	− 1	0.0678
21	− 1	0.0001	1	0.0001
22	1	0.0001	− 1	0.0000
23	− 1	0.0035	− 1	0.0086
24	− 1	0.0045	− 1	0.0000
25	1	0.9672	− 1	0.0042
26	− 1	0.0440	− 1	0.0001
27	− 1	0.0014	− 1	0.0000
28			− 1	0.0000
29	− 1	0.9045	1	1.0000
30	− 1	0.0742	1	0.0010
31	− 1	0.5134	1	0.5296
32	− 1	0.0050	− 1	0.0020
33	1	0.5627	1	0.4992
34	− 1	0.8743	− 1	0.5724
35	1	0.0006	− 1	0.0015
36	1	0.3274	1	0.0006
37	1	0.0659	1	0.0004
38	1	0.0518	1	0.0080
39	− 1	0.2376	− 1	0.6804
40	− 1	0.0024	− 1	0.0691
41			1	0.8922
42	1	0.7589	− 1	0.4872

Figure 3 HOMO orbitals for xanthones.

Table VII.  Observed Log IC₅₀ versus estimated.

Compound	LogIC50(Obs)	LogIC50(Calc)
1	− 7.57E-02	− 0.1565
2	− 0.50864	0.27088
3	− 4.58E-02	− 0.10925
4	0.57978	0.57756
5	0.72428	0.94419
6	4.14E-02	− 0.41498
7	− 0.74473	− 0.62585
8	0.11394	9.28E-02
9	1.4771	1.1997
10	− 0.13668	8.93E-02
11	0.65321	0.73208
12	1.3617	1.3959
13	− 0.95861	− 1.0924
14	1.301	1.2701
15	1.5563	1.4892
16	1.7076	1.1112
17	1.2553	0.9801
18	1.8129	1.6629
19	1.4914	2.0751
20	0.57978	0.55389
21	− 1.3979	− 0.62082
22	1.4624	1.7905
23	1.7634	1.9745
24	0.63347	0.74732
25	0.5682	0.51014
26	1.4314	0.8154
27	1.1761	1.1358
28	1.5682	1.1675
29	0.51851	− 0.12478
30	1.6021	1.3739
31	0.43136	0.81976
32	1.7076	1.4114
33	1.5682	1.6192
34	0.90309	0.64607
35	1.1139	1.158
36	− 0.18046	0.3633
37	1.3802	1.1962
38	0.92942	1.3671
39	1.2788	0.84322
40	1.3979	1.6668
41	1.3802	1.2964
42	1.5051	1.411

Figure 4 Observed Log IC₅₀ versus estimated.