Prediction of the relationship between the structural features of andrographolide derivatives and α-glucosidase inhibitory activity: A quantitative structure-activity relationship (QSAR) Study

Figures & data

Table 1.  Structure and α-glucosidase inhibitory activity of the andrographolide derivatives.

Comp code	Structure	% Inhibition /IC50 µM	Comp Code	Structure	% Inhibition /IC50 µM
AT1		34	AT2		16.5
AT3		6.9	AT4		13.2
AT5		17.1	AT6		58
AT7		84	AT8		16.7
AT9		70	AT10		16
AT11		82	AT12		100
AT13		28	AT14		16
AT15		6	AT16		14
AT17		25	AT18		36
AT19		11	A		NIa
B		NI	C		NI
D		NI	E		NI
F		NI	G		NI

Note: % Inhibition determined at 100 µM concentration.

Table 2.  Correlation matrix for the descriptors contributed in the selected QSAR models.

Descriptor	Petitjean	GCUT_PEOE2	Q_VSA_FPNEG	PM3_LUMO	SlogP_VSA2	Vsurf_Wp7	pIC50
Petitjean	1.0000	0.3897	0.0731	0.1491	0.1433	0.4474	0.4929
GCUT_PEOE2	0.3897	1.0000	0.0752	−0.4073	−0.1929	−0.0938	−0.3377
Q_VSA_FPNEG	0.07317	0.0752	1.0000	0.2231	−0.2112	0.5149	0.0902
PM3_LUMO	0.1491	−0.4073	0.2231	1.0000	0.0668	0.6623	0.6339
SlogP_VSA2	0.1433	−0.1929	−0.2112	0.0668	1.0000	−0.3866	0.2176
Vsurf_Wp7	0.4474	−0.0938	0.5149	0.6623	−0.3866	1.0000	0.6693
pIC50	0.4929	−0.3377	0.0902	0.6339	0.2178	0.6693	1.0000

Table 3.  Redundancy (Tolerance and VIF) and Durbin-Watson value of the models and descriptors.

Model	Variable	Tolerance	R^2	VIF	D-W	D-W (Tab)
Model 1	SlogP_VSA2	0.8506	0.1494	1.1757	2.0073	(0.967–1.685)
	Vsurf_Wp7	0.8506	0.1494	1.1757
Model 2	Q_VSA_FPNEG	0.7348	0.2652	1.3610	1.8557	(0.859–1.848)
	SlogP_VSA2	0.8504	0.1496	1.1760
	Vsurf_Wp7	0.6541	0.3459	1.5287
Model 3	Petitjean	0.9782	0.0218	1.0223	1.6899	(0.897–1.710)
	PM3_LUMO	0.9782	0.0218	1.0223
Model 4	Petitjean	0.6997	0.3003	1.4292	1.7586	(0.779–1.900)
	GCUT_PEOE2	0.6068	0.3932	1.6479
	PM3_LUMO	0.7455	0.2545	1.3414

DW (Tab): Tabulated Durbin-Watson values at 5% significance level.

Table 4.  Predicted activity and Cook’s distance for the molecules.

Comp code	OA	Model 1		Model 2		Model 3		Model 4
		PA	CD	PA	CD	PA	CD	PA	CD
AT1	−0.29	−0.24	0.013	−0.10	0.2291	0.02	0.4881	−0.27	0.0936
AT 2	−0.7	−0.39	0.4546	−0.64	0.0449	−0.86	0.0227	−0.93	0.0779
AT 3	−1.13	−1.05	0.0068	−1.22	0.0157	−1.45	0.3282	−1.08	0.019
AT 4	−0.82	−1.05	0.0514	−0.97	0.0269	−1.09	0.1094	−0.75	0.0188
AT 5	−0.69	−1.06	0.0974	−1.06	0.0968	−1.06	0.1298	−0.66	0.0024
AT 6	−1.76	−1.72	0.0017	−1.71	0.0025	−1.68	0.0052	−1.94	0.0786
AT 7	−0.7	−1.06	0.091	−0.81	0.0305	OL		−0.99	0.3426
AT 8	−1.92	−1.72	0.0358	−1.64	0.0799	−1.75	0.027	−1.96	0.0026
AT 9	−1.85	−1.72	0.0135	−1.57	0.1025	−1.58	0.0381	−1.58	0.0643
AT 10	−1.2	−1.72	0.226	−1.67	0.1946	−1.6	0.0901	OL
AT 11	−1.91	−1.72	0.0322	−1.88	0.0014	−1.55	0.0702	−1.67	0.0665
AT 12	−2	−1.72	0.0671	−1.96	0.0046	−1.83	0.0292	−2.06	0.011
AT 13	−1.45	−1.2	0.0299	−1.21	0.0273	−1.43	0.0001	−1.37	0.0038
AT 14	−1.2	−1.2	0	−1.17	0.0006	−1.17	0.001	−1.15	0.0044
AT 15	−0.78	−1.2	0.0869	−1.14	0.0713	OL		OL
AT 16	−1.15	−1.2	0.0014	−1.12	0.0003	−1.23	0.0099	−1.19	0.0035
AT 17	−1.39	−1.2	0.0193	−1.07	0.082	−1.14	0.0716	−1.13	0.1234
AT 18	−1.56	−1.2	0.0623	−1.44	0.0239	−1.51	0.0011	−1.7	0.0245
AT 19	−1.04	−1.2	0.0123	−1.14	0.0056	−1.15	0.014	−1.14	0.0171

OA, observed activity; PA, predicted activity; CD, Cook’s distance; OL, outlier.

Figure 1.  Scatter plot between observed and predicted for models 1–4.