ACC1/ACC2 ligands modelling using qsar method for inhibition of human ACC1/2-mediated malonyl-CoA synthesis

ACC1/ACC2  ligands modelling using qsar method for inhibition of human ACC1/2-mediated malonyl-CoA synthesis

Here, I am usingexperimental ligand value of IC50.Based on this IC50 value, I performed QSAR modelling.

Ligand

1 CC(=O)N1CCC(C(=O)N2CCC(N3CCN(C(=O)c4cc(-c5ccccc5)nc(-c5ccc6[nH]c(CN(C)C)c(C)c6c5)c4)CC3)CC2)CC1

2CC(=O)N1CCC(C(=O)N2CCC(N3CCN(C(=O)c4cc(-c5ccccc5)nc(-c5ccc6[nH]c(C)c(C#N)c6c5)c4)CC3)CC2)CC1

3COc1ccc(-c2cc(C(=O)N3CCN(C4CCN(C(=O)C5CCN(C(C)=O)CC5)CC4)CC3)cc(-c3ccc4[nH]ccc4c3)n2)cc1

4CC(=O)N1CCC(CC1)C(=O)N1CCC(CC1)N1CCN(CC1)C(=O)c1cc(nc(c1)-c1ccc(CCO)cc1)-c1ccccc1

5COc1ccc(-c2cc(C(=O)N3CCN(C4CCN(C(=O)C5CCN(C(C)=O)CC5)CC4)CC3)cc(-c3ccc4[nH]ncc4c3)n2)cc1OC

6CC(=O)N1CCC(C(=O)N2CCC(N3CCN(C(=O)c4cc(-c5ccc(C)cc5)nc(-c5ccc6[nH]ccc6c5)c4)CC3)CC2)CC1

 EXP.IC50 Actual_Activity       Pred_Activity    predict result

8.4      0.9242793          1.386696        Predicted weaker than observed

9.7      0.9867717          1.395477        Predicted weaker

 21.01.3222193          1.471803        Slightly predicted weaker

 27.01.4313638          1.512331        Slightly predicted weaker

 30.01.4771213          1.532594        Very close

 30.01.4771213          1.532594        Very close

Here, I am trying to establish relationship between molecular descriptors that predict inhibitory activity of ACC1/ACC2.

This model represents perform better toward the higher IC50/less-potent end than the low-IC50/more-potent end.