69003-01-6Relevant articles and documents
A new class of pure estrogen alpha receptor antagonists; design, synthesis and in-vitro screening
Jameera Begam, Akbar John,Basheer, Katike Ahamed,Jubie, Selvaraj,Jupudi, Srikanth,Azam, Mohammed Afzal,Dhanabal, Palanisamy
, p. 66 - 81 (2019/01/04)
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 clinical evaluation.
