In silico modeling of β-carbonic anhydrase inhibitors from the fungus Malassezia globosa as antidandruff agents

Figures & data

Figure 1. Structural detail of MG-CA inhibitors (sulfonamides) used in calibration set.

Table 1. The experimental in vitro inhibition data of MG-CA (K_I in nM), observed activity A (A = log (630 000/K_I), estimated activities, residual, standardized residual, |RStudent| and hat diagonal of the calibration set molecules 1–28 with predicted value (A), hat diagonal and their corresponding K_I in nM of the not yet synthesized ones 29–51.

Compound	KI (nM)	A (obs.)	A (est.)	Residual	Standardized residual	|RStudent|	Hat diagonal	Compound	A (predicted value)	KI (nM)	Hat diagonal
1*	9800	1.808	2.515	−0.707	−1.9589	−2.0989	0.0657	29	3.875	84.012	0.4007
2	245	3.41	3.253	0.157	0.4447	0.4368	0.1003	30	3.843	90.436	0.3173
3	152	3.617	3.872	−0.254	−0.7107	−0.7029	0.0811	31	4.391	25.606	0.3616
4	6740	1.971	2.722	−0.751	−2.1946	−2.4139	0.1589	32	3.816	96.237	0.3457
5*	174	3.559	3.316	0.243	0.683	0.6749	0.0921	33	4.65	14.104	0.5222
6	79	3.902	3.783	0.119	0.3482	0.3414	0.1679	34	4.338	28.929	0.3961
7	116	3.735	3.063	0.671	1.8563	1.9689	0.0615	35	4.731	11.704	0.5233
8	121	3.717	3.163	0.553	1.5198	1.5672	0.0496	36	4.882	8.267	0.5422
9*	349	3.257	3.326	−0.07	−0.1911	−0.1871	0.0415	37	4.779	10.479	0.4976
10	543	3.065	3.347	−0.282	−0.7728	−0.7658	0.042	38	5.094	5.074	0.5362
11	90	3.845	4.251	−0.406	−1.5229	−1.5707	0.4907	39	3.22	379.612	0.3901
12	92	3.836	3.631	0.204	0.595	0.5865	0.1544	40	3.643	143.331	0.3194
13*	79 000	0.902	0.561	0.341	1.1351	1.1426	0.3532	41	5.001	6.285	0.25
14	85 000	0.87	1.067	−0.197	−0.6688	−0.6605	0.3756	42	4.498	20.014	0.1591
15	236	3.426	3.307	0.119	0.3633	0.3563	0.2308	43	4.299	31.647	0.1291
16	104	3.782	3.476	0.306	0.9898	0.9893	0.3123	44	3.602	157.521	0.1188
17	63	4	4.073	−0.073	−0.2311	−0.2263	0.2933	45	4.251	35.346	0.1605
18*	68	3.967	3.97	−0.003	−0.0083	−0.0082	0.2387	46	3.879	83.241	0.1638
19	35 000	1.255	1.586	−0.331	−1.234	−1.2489	0.484	47	4.111	48.791	0.2237
20	234	3.43	3.431	−0.001	−0.0032	−0.0031	0.0807	48	3.6	158.248	0.0867
21	118	3.727	3.754	−0.026	−0.0761	−0.0744	0.1324	49	3.581	165.325	0.1038
22	94	3.826	3.965	−0.138	−0.4341	−0.4263	0.2705	50	4.167	42.888	0.1634
23	4530	2.143	2.138	0.006	0.016	0.0157	0.1416	51	4.185	41.147	0.3741
24*	2560	2.391	2.273	0.118	0.3409	0.3342	0.1439
25	3100	2.308	2.805	−0.497	−1.3891	−1.4194	0.0811
26	650	2.986	2.718	0.268	0.7474	0.74	0.078
27	374	3.226	2.889	0.337	0.9743	0.9732	0.1406
28*	413	3.183	2.888	0.295	0.8504	0.8451	0.1375

*Molecules of test set.

Figure 2. Structural detail of MG-CA inhibitors (sulfonamides) used in prediction set (not yet synthesized).

Figure 3. Graphs of observed versus estimated activity in the calibration set and validation set.

Table 2. Observed, estimated and residual values of MG-CA inhibitory activity (A) for the molecules used in the reduced calibration set (training set).

Compound	Obs.	Est.	Res.
2	3.41	3.273	0.137
3	3.617	3.899	−0.282
4	1.971	2.73	−0.759
6	3.901	3.82	0.081
7	3.735	3.043	0.692
8	3.716	3.154	0.562
10	3.065	3.338	−0.273
11	3.845	4.214	−0.369
12	3.835	3.621	0.214
14	0.87	0.921	−0.051
15	3.426	3.298	0.128
16	3.782	3.508	0.274
17	4	4.09	−0.09
19	1.255	1.499	−0.244
20	3.43	3.446	−0.016
21	3.727	3.786	−0.059
22	3.826	4.011	−0.185
23	2.143	2.106	0.037
25	2.308	2.771	−0.463
26	2.986	2.705	0.281
27	3.226	2.836	0.39

Table 3. Observed, estimated and residual values MG-CA inhibitory activity (A) of compound used in the validation set (test set).

Compound	Obs.	Est.	Res.
1	1.808	2.182	−0.374
5	3.558	3.259	0.299
9	3.256	2.924	0.332
13	0.902	1.101	−0.199
18	3.962	2.682	1.28
24	2.391	2.401	−0.01
28	3.178	2.804	0.374

Figure 4. |RStudent| of observed versus hat diagonal of calibration set compound.