Chiral compounds, docking

Further, there does not exist sufficient data regarding the biological activity for each enantiomer in a racemic mixture of artemisinin analogues. To help define the antimalarial contribution made by each enantiomer, a model was developed in which 40 racemates were placed as single (+)-enantiomers in the original database of 202 compounds. By doing this it was implied that the (-)-enantiomers are as active as their counterpart, and an optically pure compound is not necessary for antimalarial activity. These achiral models have been discussed as 199 (2 A/C.3) and 199 Dock. A database without the racemates, or chiral models 160 (2 A/C.3) and 160 Dock, were also included in our study. Finally, adjustment to an achiral model was attempted in which the activities of the racemates in the 199 (2 A/C.3) model were multiplied by 2, or model 199 (2 A/C.3). In each case, data was subjected to the statistical pis analysis (Table 18). Relative antimalarial activities were predicted for two racemic compounds 421 and 422,155 using these datasets as shown in Tables 19 and 20. 

These compounds have two equivalent chiral centers (C-2 and C-2 ) (Fig. 5). They have been pharmacologically evaluated as a racemic mixture (2R, 2 R/2S, 2 S) and as meso isomers (2R, 2 S). In the docking experiments the differences between the interaction modes of RR, SS, and RS isomers have been analyzed using the ligand internal energies and enzyme/hgand (E/L) interaction energies of the respective isomers with the available structures of COX-1 and COX-2 enzymes (Fig. 6, Table 4) [85]. 

The chemical databases used in docking are usually stereochemically defined within their 3D coordinates. Enantiomers are not stored. If it is necessary to invert the chiral centers for compound entry in the database, specific scripts using the function invert chiral centers should be applied. This enlarges fhe database significantly. 

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