Abstract:

AbstractUsing comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA), three dimensional structureactivity relationship(3D-QSAR) studies were carried out on a series of benzofuran N-myristoyl transferase(NMT) inhibitors. Variation of grid spacing was used during the optimization of the CoMFA model. For the CoMSIA study, the influence of the combination of different field types was evaluated and the best combination was considered to be steric, electrostatic, hydrophobic and Hbonding acceptor fields. Variation of grid spacing and attenuation factor was used to obtained the best CoMSIA model. The resulting CoMFA and CoMSIA models had a cross validated coeffiecient(q²) of 0.759 and 0.730 respectively, which showed a strong predictive ability on both test-set and trainingset. The tri-dimensional contour maps of CoMFA and CoMSIA provided smooth and interpretable explanation of the structure-activity relationship of the compounds. The analysis of the tri-dimensional contour maps permitted interesting conclusions about the effects of different substituents of different positions of the benzofuran group on the antifungal activity, which will guide the design of novel NMT inhibitors with a higher activity.

Key words: KeywordsBenzofuran; NMT inhibitors; Antifungal; 3D-QSAR; Comparative molecular field analysis(CoMFA); Comparative molecular similarity indices analysis(CoMSIA)