The role of phorbol diesters in mediating human placental aromatase cytochrome P450 activity

Odoemelam, C.S. ORCID: 0000-0002-9622-2075, Hunter, E., Eberl, D., Busi, B., Ahmad, Z., White, S. ORCID: 0000-0002-3675-7545 and Wilson, P.B. ORCID: 0000-0003-0207-2246, 2022. The role of phorbol diesters in mediating human placental aromatase cytochrome P450 activity. Applied Biosciences, 1 (3), pp. 279-288. ISSN 2813-0464

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Abstract

Due to the aromatase enzyme’s involvement in estrogen biosynthesis, aromatase inhibitors have emerged as the preferred treatment for postmenopausal women with ER+ breast cancer. Using computational chemistry tools, we investigate how the human placental aromatase cytochrome P450 interacts with various phorbols with distinct chains at C-12, C-13, and C-20, as well as the well-known aromatase inhibitors anastrozole, exemestane, and letrozole. To identify phorbol-aromatase interactions, we performed a protein–ligand docking using the structures of our ligands and proteins using the Flare software (version 2.0, Cresset Software, Litlington, UK). These preliminary findings show that the phorbols considered (P-12,13-diAcPh, P-12,13-diiBu, P-12AcPh-13iBu, P-12Ang-13iBu, P-20Ac-12AcPh-13iBu and P-20Ac-12Ang-13iBu) had the highest binding energies in comparison with the commercially available aromatase inhibitors (anastrozole, letrozole, exemestane) used in this study. A subset of the previously described binding residues of testosterone (TST), the endogenous ligand, were also found to be responsible for the phorbol diesters’ binding to the aromatase enzyme, as demonstrated by the findings. This further suggests that the phorbol diesters can bind efficiently to CYP19A1 and may be able to alter its activity because they had higher binding energies than the commercially available drugs.

Item Type: Journal article
Publication Title: Applied Biosciences
Creators: Odoemelam, C.S., Hunter, E., Eberl, D., Busi, B., Ahmad, Z., White, S. and Wilson, P.B.
Publisher: MDPI AG
Date: 2022
Volume: 1
Number: 3
ISSN: 2813-0464
Identifiers:
NumberType
10.3390/applbiosci1030017DOI
1639754Other
Rights: Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Divisions: Schools > School of Animal, Rural and Environmental Sciences
Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 25 Jan 2023 16:48
Last Modified: 25 Jan 2023 16:48
URI: https://irep.ntu.ac.uk/id/eprint/48071

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