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Natural Products with α,β-Unsaturated Carbonyl Units and Their Synthetic Derivatives: Recent Advances and Future Perspectives

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 10004

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
1. Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2. Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208 Matosinhos, Portugal
Interests: medicinal chemistry; organic synthesis; natural products; xanthones; flavonoids; antimicrobials; antitumor; antifouling
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal
Interests: medicinal chemistry; organic synthesis; drug discovery; anticancer activity; antimicrobial activity; chiral drugs; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products containing α,β-unsaturated carbonyl units (e.g., cinnamic acids, chalcones, curcuminoids and chromones) possess a wide array of biological activities, such as antimicrobial, anti-inflammatory, antitumor, antioxidant and antidiabetic, which has led to great interest as candidates for drug discovery. Otherwise, as a result of their high reactivity, α,β-unsaturated carbonyl derivatives are versatile starting materials for the synthesis of interesting bioactive compounds, namely, nitrogen heterocyclic derivatives.

This Special Issue aims to provide both recent advances and new perspectives on bioactive natural α,β-unsaturated compounds and their synthetic analogues for drug discovery. Original articles, short communications, as well as reviews of studies on this topic are welcome.

Prof. Dr. Madalena Pinto
Dr. Honorina Cidade
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • α,β-unsaturated carbonyl compounds
  • cinnamic acids
  • chalcones
  • curcuminoids
  • chromones

Published Papers (6 papers)

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Research

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16 pages, 2560 KiB  
Article
Interaction of Thiol Antioxidants with α,β-Unsaturated Ketone Moiety: Its Implication for Stability and Bioactivity of Curcuminoids
by Bo Hyun Lee, Eiseul Song and Jungil Hong
Molecules 2023, 28(23), 7711; https://doi.org/10.3390/molecules28237711 - 22 Nov 2023
Cited by 1 | Viewed by 867
Abstract
Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, the effects of different types of antioxidants on the [...] Read more.
Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, the effects of different types of antioxidants on the stability and bioactivities of curcumin were analyzed. High concentrations (>4 mM) of thiol antioxidants, including N-acetylcysteine (NAC), glutathione (GSH), and β-mercaptoethanol, accelerated the decomposition of curcumin and other curcuminoids; the submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin, regardless of their concentration. The cellular levels and bioactivities of curcumin, including its cytotoxicity and the induction of heme oxygenase-1, were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with a reduced thiol group could directly interact with the α,β-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity. Full article
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23 pages, 5307 KiB  
Article
Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights
by Emanuela Marras, Camilla J. Balacchi, Viviana Orlandi, Enrico Caruso, Maurizio F. Brivio, Fabrizio Bolognese, Maristella Mastore, Miryam C. Malacarne, Miriam Rossi, Francesco Caruso, Veronica Vivona, Nicole Ferrario and Marzia B. Gariboldi
Molecules 2023, 28(22), 7537; https://doi.org/10.3390/molecules28227537 - 11 Nov 2023
Cited by 1 | Viewed by 1050
Abstract
Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for [...] Read more.
Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical–physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising. Full article
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18 pages, 3682 KiB  
Article
Switching from Aromatase Inhibitors to Dual Targeting Flavonoid-Based Compounds for Breast Cancer Treatment
by Silvia Gobbi, Silvia Martini, Riccardo Rozza, Angelo Spinello, Jessica Caciolla, Angela Rampa, Federica Belluti, Nadia Zaffaroni, Alessandra Magistrato and Alessandra Bisi
Molecules 2023, 28(7), 3047; https://doi.org/10.3390/molecules28073047 - 29 Mar 2023
Cited by 2 | Viewed by 1505
Abstract
Despite the significant outcomes attained by scientific research, breast cancer (BC) still represents the second leading cause of death in women. Estrogen receptor-positive (ER+) BC accounts for the majority of diagnosed BCs, highlighting the disruption of estrogenic signalling as target for first-line treatment. [...] Read more.
Despite the significant outcomes attained by scientific research, breast cancer (BC) still represents the second leading cause of death in women. Estrogen receptor-positive (ER+) BC accounts for the majority of diagnosed BCs, highlighting the disruption of estrogenic signalling as target for first-line treatment. This goal is presently pursued by inhibiting aromatase (AR) enzyme or by modulating Estrogen Receptor (ER) α. An appealing strategy for fighting BC and reducing side effects and resistance issues may lie in the design of multifunctional compounds able to simultaneously target AR and ER. In this paper, previously reported flavonoid-related potent AR inhibitors were suitably modified with the aim of also targeting ERα. As a result, homoisoflavone derivatives 3b and 4a emerged as well-balanced submicromolar dual acting compounds. An extensive computational study was then performed to gain insights into the interactions the best compounds established with the two targets. This study highlighted the feasibility of switching from single-target compounds to balanced dual-acting agents, confirming that a multi-target approach may represent a valid therapeutic option to counteract ER+ BC. The homoisoflavone core emerged as a valuable natural-inspired scaffold for the design of multifunctional compounds. Full article
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11 pages, 736 KiB  
Article
Antitumor Effect of Chalcone Derivatives against Human Prostate (LNCaP and PC-3), Cervix HPV-Positive (HeLa) and Lymphocyte (Jurkat) Cell Lines and Their Effect on Macrophage Functions
by Bruno Horta, Joana Freitas-Silva, Jani Silva, Francisca Dias, Ana Luísa Teixeira, Rui Medeiros, Honorina Cidade, Madalena Pinto and Fátima Cerqueira
Molecules 2023, 28(5), 2159; https://doi.org/10.3390/molecules28052159 - 25 Feb 2023
Cited by 5 | Viewed by 2002
Abstract
Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, the effect of chalcones 118 against the metabolic viability of cervical (HeLa) and prostate (PC-3 and LNCaP) tumor cell lines was tested, to [...] Read more.
Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, the effect of chalcones 118 against the metabolic viability of cervical (HeLa) and prostate (PC-3 and LNCaP) tumor cell lines was tested, to compare the activity against solid and liquid tumor cells. Their effect was also evaluated on the Jurkat cell line. Chalcone 16 showed the highest inhibitory effect on the metabolic viability of the tested tumor cells and was selected for further studies. Recent antitumor therapies include compounds with the ability to influence immune cells on the tumor microenvironment, with immunotherapy being one actual goal in cancer treatment. Therefore, the effect of chalcone 16 on the expression of mTOR, HIF-1α, IL-1β, TNF-α, IL-10, and TGF-β, after THP-1 macrophage stimulation (none, LPS or IL-4), was evaluated. Chalcone 16 significantly increased the expression of mTORC1, IL-1β, TNF-α, and IL-10 of IL-4 stimulated macrophages (that induces an M2 phenotype). HIF-1α and TGF-β were not significantly affected. Chalcone 16 also decreased nitric oxide production by the RAW 264.7 murine macrophage cell line, this effect probably being due to an inhibition of iNOS expression. These results suggest that chalcone 16 may influence macrophage polarization, inducing the pro-tumoral M2 macrophages (IL-4 stimulated) to adopt a profile closer to the antitumor M1 profile. Full article
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13 pages, 614 KiB  
Article
Regiospecific Hydrogenation of Bromochalcone by Unconventional Yeast Strains
by Mateusz Łużny, Dagmara Kaczanowska, Barbara Gawdzik, Alicja Wzorek, Aleksandra Pawlak, Bożena Obmińska-Mrukowicz, Monika Dymarska, Ewa Kozłowska, Edyta Kostrzewa-Susłow and Tomasz Janeczko
Molecules 2022, 27(12), 3681; https://doi.org/10.3390/molecules27123681 - 8 Jun 2022
Cited by 3 | Viewed by 1542
Abstract
This research aimed to select yeast strains capable of the biotransformation of selected 2′-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2′-hydroxy-2″-bromochalcone, 2′-hydroxy-3″-bromochalcone, 2′-hydroxy-4″-bromochalcone and 2′-hydroxy-5′-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of [...] Read more.
This research aimed to select yeast strains capable of the biotransformation of selected 2′-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2′-hydroxy-2″-bromochalcone, 2′-hydroxy-3″-bromochalcone, 2′-hydroxy-4″-bromochalcone and 2′-hydroxy-5′-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2′-hydroxybromochalcones, the corresponding 2′-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances. Full article
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Review

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21 pages, 2634 KiB  
Review
Radiolabeled Chalcone Derivatives as Potential Radiotracers for β-Amyloid Plaques Imaging
by Pier Cesare Capponi, Matteo Mari, Erika Ferrari and Mattia Asti
Molecules 2023, 28(7), 3233; https://doi.org/10.3390/molecules28073233 - 4 Apr 2023
Viewed by 1804
Abstract
Natural products often provide a pool of pharmacologically relevant precursors for the development of various drug-related molecules. In this review, the research performed on some radiolabeled chalcone derivatives characterized by the presence of the α-β unsaturated carbonyl functional group as potential radiotracers for [...] Read more.
Natural products often provide a pool of pharmacologically relevant precursors for the development of various drug-related molecules. In this review, the research performed on some radiolabeled chalcone derivatives characterized by the presence of the α-β unsaturated carbonyl functional group as potential radiotracers for the imaging of β-amyloids plaques will be summarized. Chalcones’ structural modifications and chemical approaches which allow their radiolabeling with the most common SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) radionuclides will be described, as well as the state of the art regarding their in vitro binding affinity and in vivo biodistribution and pharmacokinetics in preclinical studies. Moreover, an explanation of the rationale behind their potential utilization as probes for Alzheimer’s disease in nuclear medicine applications will be provided. Full article
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