Inhibitory potential and drug-likeness of α-selinene from Syzygium aqueum, against Aromatase P450 P in breast carcinoma of Postmenopausal women: in silico study
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Date
2018
Journal Title
Journal ISSN
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Publisher
aLAKANSE PUBLISHED
Abstract
Breast cancer is the most diagnosed and prevalent cancer in women both in developed and developing countries,
this constitutes a threat to the society and world economic stability. In situ carcinoma and invasive carcinoma are the
broad rubric of breast cancer. In established breast carcinoma, about 80% depends on the gird of estrogen hormone
for growth. Hence, the down-regulation of aromatase activities has been one of the strategies used in the treatment of
breast-related carcinomas.
This study explores Syzygium aqueum for the best drug-gable compound via computation tools. Seventy-one
compounds were obtained from Syzygium aqueum plant which was retrieved from works of literature and were docked
into the active site of aromatase p450 for their antagonistic effects. Α-selinene, the lead compound with the binding
energy of -8.5 kcal/mol was obtained using PyRx, autodock vina tools used in the molecular docking to obtain the
docking scores. To ensure and validate that the right target was used, the FASTA sequence of the crystalline structure
of aromatase p450 was blast on the chembl database.
Spearman rank correlation coefficient graph was plotted on graphpad prism 6 to obtain a strong correlation (R²)
value of 0.77 between the dockings results of the CHEMBL’S compounds and their corresponding experimentally
generated IC50 results. These results explain why α-selinene should be considered a potential antagonist of aromatase
p450 in postmenopausal women suffering from breast carcinomas.
Description
Docking studies and ADMET evaluation of α-selinene with aromatase p450 showed that the ligand is a drug-gable molecule which plays critical role in the antagonism of aromatase p450, hence should be consider as a potential agent in breast cancer therapy
Keywords
Aromatase p450, Androgens, Estrogens, α-Selinene, NADPH cytochrome p450 reductase, Breast cancer, CYP19A1 gene
Citation
Oluwaseun Suleiman Alakanse, Faoziyat Adenike Sulaiman, Abiodun Julius Arannilewa, Funmilola Favour Anjorin, Oluwaseyi Israel Malachi, Ibukunoluwa Ebunolorun Ayo, Afees Adebayo Oladejo, Olutekunbi Akinwumi Oluwole, Opaleye Oyetola Olanrewaju, Usman Okeme, Ambrose Oche George, Acho Marvellous Amarachi, Oluwaseun Oluwatosin Taofeek, Olufemi Samuel Araoyinbo, Ayobamidele Abass Bakare and Tolulupe Oluwafemi Bolarinwa. (2019). Inhibitory potential and drug-likeness of α-selinene from Syzygium aqueum, against Aromatase P450 P in breast carcinoma of Postmenopausal women: in silico study. In regards to Aromatase. (aLAKANSE PUBLISHED)