Semi-synthesis as a tool for broadening the health applications of bioactive olive secoiridoids: a critical review

Oliverio, Manuela; Nardi, Mónica; Gioia, Maria Luisa Di; Costanzo, Paola; Bonacci, Sonia; Mancuso, Stefano; Procopio, Antonio

doi:10.1039/d0np00084a

Cited by 11 publications

(11 citation statements)

References 172 publications

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“…Nevertheless, secoiridoids are very sensitive molecules, in terms of chemical stability and conformational arrangements, to modifications on their functional groups. 19 For this reason, the synthetic conversion between molecules showing high similarity in their structure can be very challenging.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Based on retrosynthetic analysis, the synthesis of ligstroside starting from oleuropein seems not challenging, just replacing hydroxytyrosol by tyrosol. Nevertheless, secoiridoids are very sensitive molecules, in terms of chemical stability and conformational arrangements, to modifications on their functional groups . For this reason, the synthetic conversion between molecules showing high similarity in their structure can be very challenging.…”

Section: Resultsmentioning

confidence: 99%

“…In this context, the only secoiridoids extracted in a huge amount is oleuropein, which is largely represented in olive leaves. 18 For such reason, in recent years our research activity has been focused on the setup of sustainable semisynthetic strategies to transform oleuropein into its direct metabolites 19 such as oleacein, 20,21 oleuropein aglycone, 22 and demethyloleuropein. 23 Still meager literature exists about analogue procedures for ligstroside and its derivatives.…”

Section: ■ Introductionmentioning

confidence: 99%

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Green Semisynthetic Cascade to Ligstroside, Ligstroside Aglycone, and Oleocanthal

Mancuso

Costanzo

Bonacci

et al. 2021

ACS Sustainable Chem. Eng.

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Ligstroside, ligstroside aglycone, and oleocanthal are extra virgin olive oil (EVOO) bioactive phenols poorly represented in olive leaves. Semisynthetic pathways to achieve them, starting with largely available natural precursors, are proposed as alternative solution with respect to their low effective extraction or total synthesis. In the present work, we propose the first green chemocatalytic method to obtain, in the same semisynthetic cascade, ligstroside, ligstroside aglycone, and oleocanthal starting from oleuropein. The sustainability of the method was assessed by building the synthesis trees, while the green credentials of each step were analyzed through the CHEM21 toolkit, thus allowing consequent considerations on the large-scale feasibility.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Green Semisynthetic Cascade to Ligstroside, Ligstroside Aglycone, and Oleocanthal

Mancuso

Costanzo

Bonacci

et al. 2021

ACS Sustainable Chem. Eng.

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“…In the last few years, the N -benzylpiperidine synthon was combined with natural compounds such as ferulic acid or curcumine ( Xu et al, 2016 ; Dia et al, 2017 ) in order to obtain a new series of donepezil hybrids with potent cholinesterase inhibitory activities, radical scavenging activities and metal-chelating properties. Then, based on our experiences on the green manipulation of oleuropein and its derivatives ( Oliverio et al, 2016 ; Costanzo et al, 2018 ; Cariati et al, 2019 ; Oliverio et al, 2021 ) and the sustainable synthesis of bioactive compounds ( Costanzo et al, 2016 ; Caliandro et al, 2018 ), we decided to investigate the neuroprotective features of the olive oil polyphenols as multitarget drug candidates for the treatment of Alzheimer’s disease. Herein, we reported the design, synthesis, characterization and biological tests of new donepezil hybrids with hydroxytyrosol ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Hydroxytyrosol-Donepezil Hybrids as Potential Antioxidant and Neuroprotective Agents

et al. 2021

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It is well-accepted that the endogenous antioxidant protection system progressively decays in elderly people, and that the oxidative stress contributes to different neurodegenerative disorders such as Alzheimer’s Diseases (AD). The lower incidence of AD in countries which feature the Mediterranean Diet was associated to the high consumption of extra virgin olive oil and its polyphenolic fraction, in particular hydroxytyrosol. The protective role of these bio-phenols against oxidative stress, suggested that we combine their antioxidant/free radical scavenging activity with donepezil, an active ingredient which has just been approved for the treatment of AD. Different synthetic strategies were tested to conjugate the two different synthons in good yields. Additionally, a nitro-hydroxytyrosol derivative was synthesized to extend the application to other neurodegeneration inflammatory models. Then, their bioactivity was measured in different chemical and biological tests on a human neuroblastoma cell line (SHSY-5Y). Remarkable results on cell viability and the regulation of the redox state of cells were obtained. All hybrids showed negligible cell death under 1 μM and are stable and non toxic. Reactive oxygen species (ROS) measurements showed that the nitro-hybrid was the more effective one at reducing the ROS amount to physiological values. Then, in light of the bio-metal hypothesis of diverse neurodegenerative disorders, we tested these new compounds on the chelation properties of redox-active metals. The nitro-hybrid was able to chelate all of the tested metal cations, suggesting that we propose it as potential lead compound for a new class of neuroprotective antioxidant agents.

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“…Hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol; HT) belongs to the family of ortho-diphenolic compounds, derived from the hydrolysis of the secoiridoid oleuropein, and displays an amphiphilic character. HT acts as a natural antioxidant due to its catechol moiety, and assumes a protective role especially in bulk oils; moreover, HT has been largely investigated owing to its beneficial effects on human health, particularly in relation to cardiovascular diseases, microbial infections and cancer [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells

Todoerti

Cantafio

Oliverio

et al. 2021

IJMS

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Polyphenols from olive oil are endowed with several biological activities. Chemical modifications have been recently applied to these compounds to improve their therapeutic activity in different pathological settings, including cancer. Herein, we describe the in vitro effects on multiple myeloma (MM) cells of oleil hydroxytyrosol (HTOL), a synthetic fatty ester of natural hydroxytyrosol with oleic acid. HTOL reduced the viability of various human MM cell lines (HMCLs), even when co-cultured with bone marrow stromal cells, triggering ER stress, UPR and apoptosis, while it was not cytotoxic against healthy peripheral blood mononuclear cells or B lymphocytes. Whole-transcriptome profiling of HTOL-treated MM cells, coupled with protein expression analyses, indicate that HTOL antagonizes key survival pathways for malignant plasma cells, including the undruggable IRF4–c-MYC oncogenic axis. Accordingly, c-MYC gain- and loss-of-function strategies demonstrate that HTOL anti-tumor activity was, at least in part, due to c-MYC targeting. Taken together, these findings underscore the anti-MM potential of HTOL, providing the molecular framework for further investigation of HTOL-based treatments as novel anti-cancer agents.

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Semi-synthesis as a tool for broadening the health applications of bioactive olive secoiridoids: a critical review

Abstract: Semi-synthesis is an effective strategy to obtain both natural and synthetic analogues of the olive secoiridoids, starting from easy accessible natural compounds.

Cited by 11 publications

References 172 publications

Green Semisynthetic Cascade to Ligstroside, Ligstroside Aglycone, and Oleocanthal

Green Semisynthetic Cascade to Ligstroside, Ligstroside Aglycone, and Oleocanthal

Novel Hydroxytyrosol-Donepezil Hybrids as Potential Antioxidant and Neuroprotective Agents

Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells

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