In-silico study of novel dimeric flavonoid (OC251FR2) isolated from the seeds of Heckel () against alpha estrogen receptor (ER-α) of breast cancer.

Unlabelled: Estrogen hormone dependence accounts for a major cause in the incidence of women breast cancer. ER- is the major ER subtype in the mammary epithelium and plays a critical role in breast cancer progression. Tamoxifen (1-[4-(2-dimethylaminoethoxy)-phenyl]-1,2- diphenylbut-1(Z)-ene) is a nonsteroidal antiestrogen prodrug which formed pharmacologically active metabolite, 4-hydroxytamoxifen, largely used for endocrine therapy in pre and postmenopausal women with ER-positive breast cancer. However, long term treatment with tamoxifen results in acquires resistance and high probability of disease recurring, hence the need for an alternative breast cancer drug. In silico approach was used to investigate the inhibitory activities of a novel dimeric flavanonol OC251FR2 (3,3'-oxybis(5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one)-3,3'-oxybis(5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) isolated from the chloroform fraction of , against alpha Estrogen receptor (ER-α); a major contributor to the growth of breast cancer. The docking was conducted using Maestro module 13.5 to obtained the ER-α PDB (5W9C) from NCBI. The OC251FR2 was docked using ligprep module with 4-hydroxytamoxifen being the reference drug. The qikpro was used to investigate the drug-likeliness while ligand docking and induced fit docking were used to investigate the interaction and binding affinity of the ligands with the active sites of the PDB. The result shows that the isolated OC251FR2 with docking score value of -6.214 interact more with amino acids in the active sites via H-bond, pi-pi interaction than the reference drug 4-Hydroxytamoxifen with a docking score value of -5.289. The drug-likeliness determined by qikpro shows that OC251FR2 violated three of the Lipinski rules of 5, and also have percent oral absorption. The quantum mechanics values show that OC251FR2 have similar properties comparable to the reference drug 4-hydroxytamoxifen. Hence, can serve as potential lead against alpha Estrogen receptor (ER-α).

Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00282-5.