2D QSAR studies of the inhibitory activity of a series of substituted purine derivatives against c-Src tyrosine kinase

Peer review under responsibility of Taibah University

Figures & data

Table 1 Structure, and biological activity of purine derivatives as c-Src tyrosine kinase..

S. no	Compound no. R1 = 1–2 and R = 3–34	R2	R3	IC50	pIC50	Set
1			H	2.43	5.614	Training
2			H	2.42	5.616	Training
3	3-Methoxy	H	H	1.21	5.917	Test
4	4-Chloro	H	H	1.18	5.928	Training
5	4-Bromo	H	H	1.76	5.754	Training
6	4-Nitro	H	H	1.4	5.853	Test
7	3-Nitro	H	H	0.95	6.022	Training
8	4-Aminosulfonyl	H	H	1.82	5.739	Test
9	3-Aminosulfonyl	H	H	0.1	7.000	Training
10	4-Carbamoyl	H	H	2.2	5.657	Test
11	4-Acetamido	H	H	1.05	5.978	Training
12	H	H	H	0.75	6.124	Training
13	4-Methoxy	H	H	0.13	6.886	Training
14	3-Methoxy	H	H	0.93	6.031	Training
15	3-Methyl	H	H	0.83	6.08	Training
16	4-Chloro	H	H	0.34	6.468	Training
17	4-Bromo	H	H	0.45	6.346	Training
18	4-Nitro	H	H	0.39	6.408	Training
19	3-Nitro	H	H	0.13	6.886	Test
20	4-Aminosulfonyl	H	H	0.02	7.698	Training
21	3-Aminosulfonyl	H	H	0.12	6.92	Training
22	4-Carbamoyl	H	H	2.01	5.696	Training
23	4-Acetamido	H	H	0.65	6.187	Test
24	H	H	H	3.14	5.503	Training
25	4-Methoxy	H	H	1.33	5.876	Training
26	3-Methoxy	H	H	1.2	5.92	Training
27	3-Methyl	H	H	2.55	5.602	Test
28	4-Chloro	H	H	0.69	6.161	Training
29	4-Nitro	H	H	0.78	6.107	Training
30	3-Nitro	H	H	0.34	6.468	Training
31	4-Aminosulfonyl	H	H	0.26	6.585	Test
32	3-Aminosulfonyl	H	H	0.34	6.468	Training
33	4-Carbamoyl	H	H	1.22	5.913	Training
34	4-Acetamido	H	H	1.59	5.798	Training

Table 2 Correlation matrix between descriptors present in the best QSAR model-1.

Parameter	SsCH3E-index	H-Donor count	T_2_Cl_3	SsOHcount
SsCH3E-index	1.0000
H-Donor count	0.3276	1.0000
T_2_Cl_3	0.2047	0.5287	1.0000
SsOHcount	0.4864	0.6188	0.8064	1.0000

Table 3 Observed and predicted activities with residue according to 2D QSAR models.

Com	pIC50	2D QSAR model-1		2D QSAR model-2		2D QSAR model-3
		Pred.	Res.	Pred.	Res.	Pred.	Res.
1	5.614	5.569	0.045	5.72	−0.106	5.529	0.085
2	5.616	5.636	−0.02	5.599	0.017	5.667	−0.051
3	5.917	5.862	0.055	5.943	−0.026	5.822	0.095
4	5.928	5.965	−0.037	5.863	0.065	5.869	0.059
5	5.754	5.649	0.105	5.708	0.046	5.622	0.132
6	5.853	5.914	−0.061	5.821	0.032	5.808	0.045
7	6.022	6.173	−0.151	6.14	−0.118	5.941	0.081
8	5.739	5.691	0.048	5.648	0.091	5.631	0.108
9	7.000	7.082	−0.082	7.119	−0.119	6.845	0.155
10	5.657	5.594	0.063	5.579	0.078	5.519	0.138
11	5.978	5.888	0.09	5.917	0.061	5.754	0.224
12	6.124	6.178	−0.054	6.065	0.059	6.019	0.105
13	6.886	6.814	0.072	6.79	0.096	6.797	0.089
14	6.031	6.195	−0.164	5.973	0.058	5.931	0.100
15	6.080	5.993	0.087	5.932	0.148	5.889	0.191
16	6.468	6.307	0.161	6.249	0.219	6.247	0.221
17	6.346	6.215	0.131	6.142	0.204	6.111	0.235
18	6.408	6.252	0.156	6.287	0.121	6.316	0.092
19	6.886	6.75	0.136	6.622	0.264	6.717	0.169
20	7.698	7.583	0.115	7.729	−0.031	7.501	0.197
21	6.920	6.881	0.039	6.825	0.095	6.793	0.127
22	5.696	5.541	0.155	5.765	−0.069	5.569	0.127
23	6.187	6.014	0.173	6.248	−0.061	6.063	0.124
24	5.503	5.435	0.068	5.312	0.191	5.404	0.099
25	5.876	5.799	0.077	5.727	0.149	5.75	0.126
26	5.920	5.896	0.024	2.815	3.105	5.792	0.128
27	5.602	5.579	0.023	5.549	0.053	5.461	0.141
28	6.161	6.113	0.048	6.107	0.054	6.035	0.126
29	6.107	6.154	−0.047	6.062	0.045	6.089	0.018
30	6.468	6.345	0.123	6.251	0.217	6.367	0.101
31	6.585	6.495	0.09	6.673	−0.088	6.363	0.222
32	6.468	6.424	0.044	6.375	0.093	6.288	0.18
33	5.913	5.867	0.046	5.793	0.12	5.769	0.144
34	5.798	5.695	0.103	5.642	0.156	5.667	0.131