Traditional drug discovery methods have a basis in trial-and-error. In contrary, rational drug design approaches attempt to modulate
specific structural features with the hope for a better therapeutic value. Typically, the quantitative structure activity relationship
(QSAR) is one of the most widely used molecular modelling technique. Lantadenes are bioactive compounds derived from the
Lantana camara showing anticancer potentials. But so far, no 2D and 3D-QSAR studies have been reported. Utilizing the advantage
of this technique, in the present study, two and three-dimensional QSAR of lantadene derivatives have been developed for anticancer
activity against A549 cell lines. The regression coefficient (r2), internal cross-validation regression coefficient (q2) and external crossvalidation
regression coefficient (pred_r2) of derived QSAR models were 0.87, 0.81 and 0.82 respectively. Furthermore, in order to
highlight the key structural controlling regions and different active and inactive sites, field points-based descriptors were used to
develop a 3D-QSAR model by aligning known active compounds on to identified pharmacophore template. The derived LOO validated
PLS regression QSAR model showed acceptable r2 0.81% and q2 0.78%. Hence, this method suggests the key structural features/
consideration in designing of lantadenes as potential anticancer agents.
Keywords
Lantadene, Anticancer, NF-kB, QSAR