Quantitative structure-activity relationships studies of antioxidant hexahydropyridoindoles and flavonoid derivatives

Figures & data

Table I.  Structures and antioxidant activities (pIC₅₀) of hexahydropyridoindoles derivatives.

Compounds	R1	R2	R3	R4	R5	pIC50
1	CH3	H	H	CH3	H	4.60
2	CH3	NO2	H	CH3	H	4.58
3	CH3	Br	H	CH3	H	4.80
4	CH3	NH2	H	CH3	H	4.90
5	CH3	N(CH3)2	H	CH3	H	4.66
6	CH3	H	H	OH	H	4.68
7	CH3	H	H	OCH3	H	4.48
8	CO-O-i-Bu	H	H	OCH3	H	5.12
9	CO-O-CH3	Br	CH3	OCH3	CH3	4.71
10	CO-O-CH3	H	CH3	OCH3	CH3	4.71
11	CO-O-Et	H	CH3	OCH3	CH3	4.70
12	CO-O-Pr	H	CH3	OCH3	CH3	5.16
13	CO-O-Bu	H	CH3	OCH3	CH3	5.35
14	CO-O-i-Bu	H	CH3	OCH3	CH3	5.19
15	CO-O-CH2-Ph	H	CH3	OCH3	CH3	5.48
16	CO-O-CH2-P	H	H	OCH3	H	5.49
17	CO-O-CH2-P	CH3	H	OCH3	H	5.29
18	CO-O-CH2-P	CH3	H	CH3	H	5.36
19	CO-O-CH2-P	CH3	CH3	Br	H	5.53

Table II.  Structures and antioxidant activities (pIC₅₀) of flavonoid derivatives.

Compounds	R1	R2	OH position	pIC50
20	C6H3-3,4′-OH	OH	5,7	4.43
21	C6H4-4′-OH	H	5,7	4.16
22	C6H4-3′-OH	H	5,7	4.28
23	C6H4-4′-OCH3	H	6	3.86
Compounds	R1	R2	OH position	pIC50
24	C6H3-3′,4′-OH	OH	3,5,7	4.93
25	C6H3-2′,4′-OH	OH	3,5,7	4.24
26	C6H5	OH	3,5,7	3.92
27	C6H5	H	6	3.72
28	C6H5	H	7,8	4.22
29	C6H5	H	5,7	4.17
30	C6H5	H	5,6,7	3.80
31	H	C6H4-4′-OH	7	4.10

Figure 1 Distribution of pIC₅₀ of the compounds.

Figure 2 Distributions of chemical families (a) and biological activities (pIC₅₀) (b) versus number of compounds for the training (black) and test (grey) sets of model 1.

Table III.  Statistical results for the five 2D-QSAR models.

	Model 1	Model 2	Model 3	Model 4	Model 5
q^2 ^a	0.794	0.876	0.890	0.898	0.880
N ^b	2	5	2	3	2
scv ^c	0.213	0.209	0.203	0.185	0.209
r^2 ^d	0.888	0.929	0.931	0.934	0.929
s ^e	0.157	0.158	0.161	0.148	0.161
F ^f	71.708	39.245	121.992	80.705	117.327
r^2pred ^g	0.952	0.918	0.907	0.901	0.939

^aCrossvalidation correlation coefficient

^bNumber of components

^cStandard error of prediction

^dCorrelation coefficient

^eStandard error of estimate

^fF-ratio

^gPredicted correlation coefficient.

Table IV.  Predicted values versus actual values for the test set of model 1.

Compounds	Experimental pIC50	Predicted pIC50	Difference
5	4.66	4.68	0.02
13	5.35	5.26	0.09
14	5.19	5.27	0.08
18	5.36	5.36	0.00
19	5.53	5.36	0.17
22	4.28	4.10	0.18
23	3.86	4.00	0.14
27	3.72	3.91	0.19
28	4.22	4.00	0.22
30	3.80	4.00	0.20

Figure 3 Predicted values versus experimental values for the training (a) and test (b) sets of model 1. General structure of 1,2,3,4-tetrahydro-β-carbolines R₁, R₂ = alkyl groups.

Table V.  Values of the 5 descriptors chosen.

Compounds	χ2	ICR	IC5	nCT	nCO
1	6.00	1.00	4.00	0.00	0.00
2	8.00	2.00	4.00	0.00	0.00
3	7.00	1.00	4.00	0.00	0.00
4	7.00	1.00	4.00	0.00	0.00
5	8.00	2.00	4.00	0.00	0.00
6	6.00	1.00	4.00	0.00	0.00
7	7.00	2.00	4.00	0.00	0.00
8	9.00	2.00	4.00	1.00	0.00
9	9.00	2.00	4.00	0.00	0.00
10	9.00	2.00	4.00	0.00	0.00
11	9.00	2.00	4.00	0.00	0.00
12	9.00	2.00	5.00	0.00	0.00
13	10.00	2.00	5.00	0.00	0.00
14	10.00	2.00	4.00	1.00	0.00
15	11.00	2.00	5.00	0.00	0.00
16	10.00	2.00	5.00	0.00	0.00
17	11.00	2.00	5.00	0.00	0.00
18	11.00	2.00	5.00	0.00	0.00
19	11.00	2.00	5.00	0.00	0.00
20	10.00	2.00	5.00	0.00	1.00
21	10.00	2.00	5.00	0.00	1.00
22	10.00	2.00	5.00	0.00	1.00
23	8.00	2.00	4.00	0.00	1.00
24	7.00	2.00	4.00	0.00	1.00
25	8.00	2.00	4.00	0.00	1.00
26	8.00	2.00	4.00	0.00	1.00
27	8.00	2.00	4.00	0.00	1.00
28	9.00	2.00	4.00	0.00	1.00
29	9.00	2.00	4.00	0.00	1.00
30	8.00	2.00	4.00	0.00	1.00
31	8.00	2.00	4.00	0.00	1.00