| Title: |
Anticancer Effect of Nature-Inspired Indolizine-Based Pentathiepines in 2D and 3D Cellular Model |
| Authors: |
Roberto Tallarita; Federica Randisi; Lukas Manuel Jacobsen; Emanuela Marras; Mattia Riva; Giulia Modoni; Johannes Fimmen; Siva Sankar Murthy Bandaru; Carola Schulzke; Marzia Bruna Gariboldi |
| Contributors: |
Tallarita, Roberto; Randisi, Federica; Manuel Jacobsen, Luka; Marras, Emanuela; Riva, Mattia; Modoni, Giulia; Fimmen, Johanne; Sankar Murthy Bandaru, Siva; Schulzke, Carola; Gariboldi, Marzia Bruna |
| Publication Year: |
2025 |
| Collection: |
IRInSubria - Institutional Repository Insubria (Università degli Studi dell’Insubria) |
| Subject Terms: |
pentathiepine; polysulfide; molybdenum; S-heterocycle; indolizine; 2D and 3D cell model; cell death; migration; sulfide production |
| Description: |
Background: 1,2,3,4,5-pentathiepines (PTEs) are compounds originally identified in marine ascidians and are currently under investigation for their promising pharmacological properties, particularly as potential antineoplastic agents. Objectives: In this study, we investigated the antineoplastic properties of a series of ten indolizine-based PTEs, comprising eight previously reported compounds and two newly synthesized derivatives. Methods: These compounds were evaluated against a panel of human cancer cell lines of diverse tissue origins, as well as, for the first time, on non-cancerous CR9 fibroblasts to assess their cytotoxic selectivity. In addition, their effects were tested on 3D spheroid models, providing preliminary insights into their potential in vivo efficacy. Initial screening focused on cell viability, followed by a more detailed characterization of the most active compounds in terms of their ability to induce apoptosis, necrosis, cell cycle arrest, and reactive oxygen species (ROS) generation. The anti-migratory activity of PTEs and a newly adapted assay to confirm sulfur species release in the cells were also performed for the first time. Results and Conclusions: Our findings reveal that four PTEs bearing hydrophilic, hydrogen-bonding functional groups, particularly the two inspired by natural analogs, exhibited the most potent anticancer activity. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40723276; info:eu-repo/semantics/altIdentifier/wos/WOS:001539701100001; volume:17; issue:14; firstpage:1; lastpage:23; numberofpages:23; journal:CANCERS; https://hdl.handle.net/11383/2196031 |
| DOI: |
10.3390/cancers17142393 |
| Availability: |
https://hdl.handle.net/11383/2196031; https://doi.org/10.3390/cancers17142393; https://www.mdpi.com/2072-6694/17/14/2393 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B2A60B95 |
| Database: |
BASE |