Design of Novel <i>N</i>-Myristoyltransferase Inhibitors of <i>Leishmania donovani</i> Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis

Letícia Santos-Garcia

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Daniela R. Silva

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Letícia C. Assis

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Tamiris M. de Assis

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Giovanna C. Gajo

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Ítalo Antônio Fernandes

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Teodorico C. Ramalho

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

Elaine F. F. da Cunha ^**e-mail: elaine_cunha@dqi.ufla.br

Departamento de Química, Universidade Federal de Lavras, PO Box 3037, 37200-000 Lavras-MG, Brazil

No.	pIC₅₀	No.	pIC₅₀
1	6.30	2	6.22
3	5.46	4	6.10
5	5.38	6	5.03
7	4.63	8	5.37
9	5.80	10	5.15
11	5.15	12	6.00
13	6.68	14	6.77
15	6.48	16	5.80
17	5.52	18	6.51
19	6.15	20	5.80
21	5.62	22	5.40
23	6.15	24	5.82
25	6.30	26	7.18
27	7.36	28	6.85
29	6.10	30	7.15
31	6.82	32	6.52
33	6.00	34	5.68
35	7.34	36	7.51
37	7.14	38	6.41
39	7.08	40	6.62
41	6.55	42	4.47
43	3.87	44	5.24
45	4.52	46	4.29
47	5.47	48	5.28
49	4.69	50	4.77
51	5.35	52	5.11
53	6.06	54	6.34
55	4.42	56	4.25
57	4.66	58	4.66
59	5.80	60	6.57
61	7.70	62	7.07
63	7.30	64	6.41
65	7.00	66	6.77
67	5.32	68	6.17
69	5.68	70	7.00
71	5.51	72	6.89
73	6.19	74	5.35
75	7.76	76	8.00
77	7.15

Alignment	R²	q²	q²_adj	LSE	LOF	R²_Pred	r²_{m (test)}	R²_r	R² _p	GCODs
A1	0.76	0.70	0.65	0.21	0.39	0.74	0.54	0.11	0.61	5
A2	0.73	0.66	0.61	0.22	0.49	0.82	0.48	0.09	0.68	5
A3	0.74	0.69	0.64	0.24	0.52	0.67	0.45	0.08	0.70	5
A4	0.69	0.69	0.64	0.24	0.52	0.67	0.45	0.09	0.70	5
A5	0.72	0.66	0.61	0.24	0.72	0.73	0.51	0.08	0.68	5
A6	0.74	0.68	0.63	0.23	0.41	0.75	0.45	0.07	0.71	5
A7	0.71	0.64	0.59	0.24	0.53	0.77	0.58	0.10	0.66	5

Alignment	R²	q²	q²_adj	LSE	LOF	R²_Pred	r²_{m (test)}	R²_r	R²_p	GCODs
B1	0.74	0.69	0.64	0.20	0.37	0.69	0.52	0.08	0.71	5
B2	0.72	0.66	0.61	0.23	0.50	0.78	0.55	0.08	0.68	5
B3	0.70	0.63	0.59	0.24	0.53	0.77	0.55	0.08	0.65	5
B4	0.64	0.57	0.54	0.28	0.59	0.76	0.44	0.08	0.60	4
B5	0.72	0.66	0.61	0.22	0.49	0.78	0.58	0.08	0.68	5
B6	0.70	0.64	0.59	0.22	0.41	0.83	0.63	0.08	0.66	5
B7	0.73	0.67	0.62	0.24	0.52	0.69	0.49	0.08	0.69	5

Alignment	R²	q²	q²_adj	LSE	LOF	R²_Pred	r²_{m (test)}	R²_r	R² _p	GCODs
C1	0.74	0.68	0.63	0.21	0.38	0.74	0.57	0.07	0.70	5
C2	0.72	0.65	0.60	0.23	0.50	0.75	0.52	0.08	0.67	5
C3	0.71	0.64	0.59	0.25	0.60	0.65	0.33	0.11	0.65	5
C4	0.71	0.65	0.60	0.23	0.51	0.66	0.37	0.12	0.65	5
C5	0.73	0.66	0.61	0.22	0.49	0.72	0.46	0.09	0.68	5
C6	0.75	0.69	0.64	0.22	0.49	0.64	0.51	0.08	0.70	5
C7	0.72	0.65	0.60	0.24	0.52	0.73	0.56	0.08	0.67	5

	(0,-2,4,1)	(0,3,2,0)	(3,-2,-1,1)	(0,-3,2,0)	(0,4,-1,0)
(0,-2,4,1)	1
(0,3,2,0)	0.245	1
(3,-2,-1,1)	-0.403	-0.416	1
(0,-3,2,0)	-0.324	0.069	0.098	1
(0,4,-1,0)	-0.27	0.222	-0.037	-0.216	1

\begin{matrix} {pIC}_{50} = 5.76 + 1.19 (0, - 2, 4 np) - 0.56 (0, 3, 2, any) + \\ 1.46 (3, - 2, - 1, np) + 2.03 (0, - 3, 2, any) - 0.95 (0, 4, - 1 any) \\ n = 58, GCODs = 5, R^{2} = 0.76, q^{2} = 0.70, q_{adj}^{2} = 0.65, \\ LSE = 0.21, LOF = 0.39, \\ R_{pred}^{2} = 0.74, r_{m (test)}^{2} = 0.54, R_{r}^{2} = 0.11, R_{p}^{2} = 0.61 \end{matrix}

Brasil