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Synthesis of Bioactive Compounds, 3rd Edition

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 703

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania
Interests: cancer therapy; anti-infective drugs; molecular mechanisms; drug synthesis; targeted therapies; bioactive heterocycle synthesis; docking and molecular modelling
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Special Issue Information

Dear Colleagues,

In recent decades, the emergence of new highly pathogenic strains of viruses and microorganisms, such as SARS-CoV-2, drug-resistant tuberculosis, and malaria (i.e., superbugs), has presented challenges that require an urgent response. The effective treatment of cancer is another important and unresolved problem. Tumors develop through genetic and epigenetic changes that modify fundamental cellular programs for growth and proliferation, followed by the natural selection of reprogrammed cells that best adapt to the constant fight against human immunity and chemotherapy drugs.

To address these issues, a number of breakthrough synthetic methodologies need to be developed which enable the efficient assembly of new molecules and make it possible to achieve the high variability of substituents necessary for studying structure–biological activity relationships.

This Special Issue aims to gather scientific articles devoted to the synthesis and study of the activity of previously unknown compounds, as well as fully synthetic papers that describe new effective approaches to known biologically active compounds, without further evaluation of the biological properties.

Prof. Dr. Brindusa Tiperciuc
Guest Editor

Manuscript Submission Information

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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

  • biological activity
  • nature-derived molecules
  • heterocyclic moieties
  • aromatic species
  • structural diversity
  • alkaloids
  • organic synthesis

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Published Papers (2 papers)

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Research

18 pages, 1984 KiB  
Article
Discovery of MAGL Inhibition by Lophine Derivatives: An Unexpected Finding from Chemiluminescent Assay Development
by Roberta Ottria, Silvana Casati, Ornella Xynomilakis, Aleksandar Veselinović and Pierangela Ciuffreda
Molecules 2025, 30(7), 1605; https://doi.org/10.3390/molecules30071605 - 3 Apr 2025
Viewed by 257
Abstract
The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development of a chemiluminescent monoacylglycerol lipase (MAGL) assay. The proposed lophine derivatives were found to exhibit concentration-dependent inhibitory effects on MAGL with the octanoic and palmitic acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole [...] Read more.
The inhibitory effects of two novel lophine derivatives were unexpectedly discovered during the development of a chemiluminescent monoacylglycerol lipase (MAGL) assay. The proposed lophine derivatives were found to exhibit concentration-dependent inhibitory effects on MAGL with the octanoic and palmitic acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole showing the strongest activity. Reversibility assays using a fluorometric method confirmed that these compounds interact with MAGL in a stable, irreversible manner. To further investigate their mode of interaction, docking studies were performed, supporting the hypothesis that compounds 3 and 4 may act as competitive and irreversible inhibitors. Lophine derivatives were initially designed and synthesized as potential chemiluminescence pro-enhancers. However, assay optimization revealed no signal production upon MAGL hydrolysis, precluding their use as chemiluminescent probes. These findings suggest that lophine is a promising candidate for the development of MAGL inhibitors, although further optimization is needed to enhance binding affinity and selectivity. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds, 3rd Edition)
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27 pages, 6210 KiB  
Article
Synthetic Epoxyeicosatrienoic Acid Mimics Protect Mesangial Cells from Sorafenib-Induced Cell Death
by Marcus de Bourg, Abhishek Mishra, Rawand S. Mohammad, Christophe Morisseau, Bruce D. Hammock, John D. Imig and Anders Vik
Molecules 2025, 30(7), 1445; https://doi.org/10.3390/molecules30071445 - 24 Mar 2025
Viewed by 330
Abstract
Nineteen potential mimics of 8,9-epoxyeicosatrienoic acid (8,9-EET), a natural bioactive oxylipin, were synthesized and evaluated for their ability to protect renal mesangial cells against sorafenib-induced cell death in a water-soluble tetrazolium (WST-8) assay. All compounds were also evaluated as inhibitors of soluble epoxide [...] Read more.
Nineteen potential mimics of 8,9-epoxyeicosatrienoic acid (8,9-EET), a natural bioactive oxylipin, were synthesized and evaluated for their ability to protect renal mesangial cells against sorafenib-induced cell death in a water-soluble tetrazolium (WST-8) assay. All compounds were also evaluated as inhibitors of soluble epoxide hydrolase. As expected of a potent pan-kinase inhibitor the drug sorafenib caused a significant decrease in cell viability in HRMCs. Several analogs containing amide and oxamide groups in place of the epoxide showed efficacy in reducing sorafenib induced human renal mesangial cell (HRMC) death. Oxamide containing analogs proved particularly effective, with the most promising analog increasing cell viability five-fold over control at 1 µM. These analogs, containing an oxamide group as a bioisostere for the epoxide in 8,9-EET, did not display significant inhibitory activity towards soluble epoxide hydrolase. This preliminary structure–activity relationship analysis reveals the oxamide group as a promising bioisostere for the epoxide in the 8,9-position of the fatty acid chain, producing protective effects against sorafenib-induced cell death in HRMCs. Collectively, these findings demonstrate the potential for using epoxide mimics and particularly oxamides as 8,9-EET analogs as bioisosteres of the corresponding epoxide in a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds, 3rd Edition)
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