Impact of tautomery of 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropanamide on the COX-1 inhibitory mechanism

Figures & data

Table 1.  Table showing 30 conformations (as S. No.) of different tautomers generated by compound 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropanamide (6a) with their respective energy of Conformation (E_con T).

S. No.	E_conf_T-1	E_conf_T-2	E_conf_T-3	E_conf_T-4	E_conf_T-5	E_conf_T-6
1	0.8	0.2	0	1.8	0.0	1.5
2	1.6	1.6	0.2	1.3	1.0	1.2
3	0.8	2.2	0.8	0.6	1.7	1.2
4	2.8	2.2	0	0.002	1.0	1.1
5	1.4	0.2	0	1.7	1.5	0.7
6	2.8	1.4	0.8	1.3	1.7	0.9
7	2.2	1.4	0.8	1.6	1.2	0.6
8	1.4	0.8	0.8	1.7	0.6	0.3
9	2.2	1.4	0.8	1.4	1.2	1.6
10	2.8	1.6	1.4	1.5	1.3	1.4
11	2.2	2.8	2.2	0.6	1.2	1.3
12	1.2	2.8	0.8	1.2	0.6	1.2
13	0.8	1.4	0	0.9	1.7	0.7
14	2.8	1.6	2.2	1.0	0.0	0.4
15	2.2	1.2	2.2	0.0	0.5	1.5
16	2.8	0.6	0.6	1.3	0.8	1.6
17	2.8	1.2	1.2	0.4	1.9	0.7
18	0.8	2.8	0.2	0.6	0.7	1.3
19	2.2	0.2	0.8	2.0	1.2	1.2
20	2.8	0.2	0.8	1.5	1.1	0.0
21	1.6	0.6	0.8	0.5	0.9	0.4
22	1.6	2.8	0	0.4	0.9	1.8
23	2.2	1.4	0.8	1.2	0.6	0.0
24	0.6	2.2	2.2	0.4	0.7	0.3
25	2.2	0.8	0.8	0.6	0.5	0.3
26	1.2	2.2	0.8	1.5	0.2	0.0
27	1.6	1.6	0.8	0.4	0.9	0.0
28	1.6	1.4	1.6	0.9	1.5	0.9
29	1.6	1.2	1.6	1.4	1.6	1.6
30	1.6	1.4	0	1.1	1.5	1.6

Where E_conf_T is the energy of conformation of tautomers 1, 2, 3, 4, 5 & 6.

S. No.− It indicates number of conformation generated by compound 6a.

Figure 1.  Structure of 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropionamide 6a.

Figure 2.  Six principal neutral possible tautomeric forms for compound 6a.

Figure 3.  Ramchandran Plot for pdb 3N8X (1) after energy and residue optimization.

Figure 4.  Connolly surface representations of the active site of COX-1 with the bound tauto-4, shown in Ball and Stick model. Connolly surface of the active site of the COX-1 is colored according to a charge spectrum: Blue colour for H-bonding region, white colour indicates lipophilic area while red colour is used to reveal mild polar area.

Figure 5.  Showing 2D hydrogen bonding interaction of tauto-4 with COX-1.

Figure 6.  Receptor based electrostatic regions in the active site of COX-1. Blue = donor, Red = acceptor and white = hydrophobic regions.