Identification of novel bioactive compounds from Olea europaea by evaluation of chemical compounds in the OliveNet™ library: in silico bioactivity and molecular modelling, and in vitro validation of hERG activity

Eleni Pitsillou; Julia J Liang; Raymond C Beh; Jacqueline Prestedge; Seda Catak; Andrew Hung; Tom C Karagiannis

doi:10.1016/j.compbiomed.2022.105247

Identification of novel bioactive compounds from Olea europaea by evaluation of chemical compounds in the OliveNet™ library: in silico bioactivity and molecular modelling, and in vitro validation of hERG activity

Comput Biol Med. 2022 Mar:142:105247. doi: 10.1016/j.compbiomed.2022.105247. Epub 2022 Jan 21.

Authors

Eleni Pitsillou¹, Julia J Liang¹, Raymond C Beh², Jacqueline Prestedge², Seda Catak³, Andrew Hung⁴, Tom C Karagiannis⁵

Affiliations

¹ Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia; School of Science, STEM College, RMIT University, VIC, 3001, Australia.
² Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3052, Australia.
³ Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
⁴ School of Science, STEM College, RMIT University, VIC, 3001, Australia.
⁵ Epigenomic Medicine, Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3052, Australia. Electronic address: tom.karagiannis@monash.edu.

PMID: 35077933
DOI: 10.1016/j.compbiomed.2022.105247

Abstract

Background: As highlighted in the OliveNet™ library, Olea europaea consists of a diverse collection of chemical compounds. We have classified over 600 compounds into 13 main classes and 47 subclasses. Various compounds, including oleuropein and hydroxytyrosol, have been investigated for their potential beneficial effects in multiple human pathologies. However, the vast majority of compounds remain largely unexplored and approximately 50% are currently non-commercially available.

Method: Here, we utilise conventional software to characterise the absorption, distribution, metabolism, excretion, and toxicity profile of OliveNet™ compounds. Molecular docking was performed for assessment of P-glycoprotein (P-gp) inhibition and interactions with the human ether-à-go-go-related gene (hERG) channel. Potential hERG ion channel inhibition was calibrated using in vitro patch clamp assays and steered molecular dynamics (SMD) simulations were used to examine membrane permeability of a subset of compounds.

Results: Our findings indicated that 313 out of 675 olive compounds were predicted to be absorbed by the gastrointestinal tract. Hydroxytyrosol required the least amount of force to pass through the lipid bilayer compared to elenolic acid diglucoside in SMD simulations. Based on the ADMET and molecular docking data, the hERG inhibitory activities of verbascoside, oleuropein, and hydroxytyrosol were investigated using patch clamp assays and they were identified as non-inhibitors.

Conclusions: While the favourable properties of well-known compounds were confirmed, we identified oleuropein aglycone decarboxymethyl dialdehyde acetal form, decarboxymethyl elenolic acid dialdehyde, acetal of decarboxymethyl elenolic acid dialdehyde, methyl malate-β-hydroxytyrosol ester, hydroxytyrosil elenolate, D-(+)-erythro-1-(4-hydroxy-3-methoxy)-214-phenyl-1,2,3-propantriol, (+)-1-acetoxypinoresinol-4″-O-methyl ether, and 3-[1-(hydroxymethyl)-(E)-1-propenyl] glutaric acid as potential candidates for synthesis and further evaluation.

Keywords: ADMET; Olea europaea; Pharmacokinetics; Phenolics; Secoiridoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Molecular Docking Simulation
Olea* / chemistry