QSAR studies on pyrazole-4-carboxamide derivatives as Aurora A kinase inhibitors

Peer review under responsibility of Taibah University.

Figures & data

Table 1 Structures and activity of pyrazole-4-carboxamide derivatives as anticancer agents..

S. No.	R1	R2	HCT116 (IC50)	pIC50	MCF-7(IC50)	pIC50	QSAR set
1	H	H	2.31	5.6363	2.34	5.6307	Training
2	H	Cl	3.52	5.4534	3.86	5.4134	Training
3	H	Br	4.47	5.3496	5.75	5.2403	Test
4	H	OMe	1.35	5.8696	1.71	5.7670	Training
5	H	OEt	0.62	6.2076	0.88	6.0555	Test
6	Me	H	2.36	5.6270	.45	6.3467	Training
7	Me	Cl	3.88	5.4111	4.01	5.3968	Training
8	Me	Br	5.35	5.2716	6.08	5.2160	Training
9	Me	OMe	1.45	5.8386	1.62	5.7904	Training
10	Me	OEt	0.78	6.1079	1.03	5.9871	Test
11	OMe	H	2.54	5.5951	2.53	5.5968	Training
12	OMe	Cl	4.06	5.3914	4.35	5.3615	Training
13	OMe	Br	5.87	5.2313	8.21	5.0856	Training
14	OMe	OMe	1.52	5.8181	1.77	5.7520	Training
15	OMe	OEt	0.97	6.0132	1.10	5.9586	Test
16	Cl	H	2.18	5.6615	2.34	5.6307	Training
17	Cl	Cl	2.99	5.5243	3.75	5.4259	Training
18	Cl	Br	4.36	5.3605	5.31	5.2749	Training
19	Cl	OMe	1.33	5.8761	1.55	5.8096	Training
20	Cl	OEt	0.42	6.3767	0.56	6.2518	Training
21	NO2	H	2.01	5.6968	2.26	5.6458	Test
22	NO2	Cl	2.92	5.5346	3.24	5.4894	Training
23	NO2	Br	4.08	5.3893	5.30	5.2757	Training
24	NO2	OMe	1.02	5.9914	1.21	5.9172	Training
25	NO2	OEt	0.39	6.4089	0.46	6.3372	Training

Table 2 Correlation matrix between descriptors present in the best QSAR model-1(HCT116-cell-lines).

Parameter	SsCH3E-index	SsBrE-index	T_2_Cl_1	2PathCount
SsCH3E-index	1.0000
SsBrE-index	0.6328	1.0000
T_2_Cl_1	0.4328	0.7123	1.0000
2PathCount	0.5241	0.6874	0.8436	1.0000

Fig. 1 (a) Contribution charts of the descriptors for the 2D model-1. (b) Plot of observed versus predicted activity by best 2D QSAR model 1. (c) Contribution charts of the descriptors for the 2D model-2. (d) Plot of observed versus predicted activity by best 2D QSAR model 2. (e) Contribution charts of the descriptors for the 2D model-3. (f) Plot of observed versus predicted activity by best 2D QSAR model 3. (g) Contribution charts of the descriptors for the 2D model-4. (h) Plot of observed versus predicted activity by best 2D QSAR model-4. (i) The designed scaffold new chemical entity.

Table 4 Comparative observed and predicted activities of carboxamide derivatives.

Com	QSAR model-1 (HCT116)		QSAR model-2 (HCT116)		QSAR model-3 (MCF-7)		QSAR model-4 (MCF-7)
	Pred.	Res.	Pred.	Pred.	Res.	Res.	Pred.	Res.
1	5.6906	−0.0543	5.3562	0.2801	5.6492	−0.0185	5.6188	0.0119
2	5.3687	0.0847	5.3947	0.0587	5.4384	−0.025	5.4017	0.0117
3	5.3758	−0.0262	5.3566	−0.007	5.3199	−0.0796	5.2165	0.0238
4	5.8861	−0.0165	5.8674	0.0022	5.7931	−0.0261	5.6863	0.0807
5	6.4197	−0.2121	6.4039	−0.1963	6.3609	−0.3054	6.2685	−0.213
6	5.6165	0.0105	5.6369	−0.0099	6.2984	0.0483	6.2017	0.145
7	5.4331	−0.022	5.4171	−0.006	5.2947	0.1021	5.1945	0.2023
8	5.4327	−0.1611	5.4160	−0.1444	5.3360	−0.12	5.2249	−0.0089
9	5.8224	0.0162	5.8296	0.009	5.6426	0.147	5.7360	0.0544
10	6.2941	−0.1862	6.0195	0.0884	5.9553	0.031	5.8615	0.1256
11	5.5570	0.0381	5.5722	0.0229	5.5565	0.0403	5.5895	0.0073
12	5.3942	−0.0028	5.3905	0.0009	5.3845	−0.023	5.3074	0.0541
13	5.3875	−0.1562	5.3664	−0.1351	5.1662	−0.0806	5.1983	−0.1127
14	5.8554	−0.0373	5.8437	−0.0256	5.7674	−0.0154	5.7036	0.0484
15	6.1224	−0.1092	6.2096	−0.1964	5.9213	0.0373	5.8990	0.0596
16	5.6542	0.0073	5.6405	0.021	5.6940	−0.0633	5.6135	0.0172
17	5.4550	0.0693	5.3380	0.1863	5.3523	0.0736	5.3320	0.0939
18	5.3920	−0.0315	5.3802	−0.0197	5.3138	−0.0389	5.2086	0.0663
19	5.7120	0.1641	5.7911	0.085	5.8272	−0.0176	5.7818	0.0278
20	6.4197	−0.043	6.3639	0.0128	6.2147	0.0371	6.1645	0.0873
21	5.6365	0.0603	5.6726	0.0242	5.6403	0.0055	5.6215	0.0243
22	5.5672	−0.0326	5.5483	−0.0137	5.2975	0.1919	5.3882	0.1012
23	5.4331	−0.0438	5.4171	−0.0278	5.3317	−0.056	5.2194	0.0563
24	5.8327	0.1587	5.8160	0.1754	5.9692	−0.052	5.8873	0.0299
25	6.3188	0.0901	6.3988	0.0101	6.3302	0.007	6.2197	0.1175

Table 3 Correlation matrix between descriptors present in the QSAR model-3(MCF-7-cell-lines).

Parameter	Chlorines count	T_N_F_3	SddsN (nitro) count
Chlorines count	1.0000
T_N_F_3	0.5931	1.0000
SddsN (nitro) count	0.6854	0.7593	1.0000