Background: In view of the estrogenic receptor inhibitory properties of coumarin
nucleus, long chain nature of fatty acid and anti-breast cancer activity of fatty acids, it was proposed
to attach long chain fatty acids at 3rd,4th and 7th position of coumarin nucleus and evaluate for their
anti-breast cancer activity through suitable in-vitro methods.
Methods: The present study focuses a library of fatty acid coumarin conjugates as ligands to the
ligand-binding domain of the human estrogen receptor α (PDB ID 2IOG) and their binding affinities
using GLIDE module of Schrodinger after ascertaining their drug-likeness with QIKPROP. The
compounds LNAC 8, SAC 1 and OAC 5 are the best hits based on their docking scores as well as
the Prime MM-GBSA free energy of binding. Based on the in-silico results and synthetic feasibility
the compounds SAC 1 PAC 1 and OAC 1 are synthesized, characterized and investigated for their
time interval growth inhibitory effect on MCF-7 which is an ER positive breast cancer cell lines.
Results: SAC 1, showed better in vitro growth inhibitory effect in sub micromolar range as
compared to Tamoxifen, a standard estrogen receptor modulator.
Conclusion: Conclusively, in silico molecular docking studies have been very useful in predicting
the pharmacokinetic profiles and the binding affinities of new hits before a detailed preclinical and