In the present study, the differential binding kinetics obtained for withanolide A (C28H38O6), withanolide B (C28H38O5), withanolide E (C28H38O7) and withanone (C28H38O7) might be attributed to the varying number of oxygen atoms in their structures which might affect hydrogen bonding within the binding site of the target protein(s). Another explanation for differential SAR obtained for the above withanolides might be due to various kinds of structural rearrangements (A or B) involving oxygen substituents like bond scission, new bond formation, ring aromatization, etc. which help in formation of novel structural variants and compounds with novel structures (Figure 5) often described as modified withanolides or ergostane type steroids (Misico et al., 2011). The structural rearrangement as seen in withanolide A and B might be responsible for a better complementary fit of the phytoconstituent in the binding pocket of the target protein(s).