Towards novel liver injury therapies based on design, synthesis and therapeutic efficacy of novel sulfone bis-compound on liver necrosis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Rashdan H.R.M.; Hassan S.; Maher S.; Okasha H.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 20 May 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 17546

ISSN: 20452322

DOI: 10.1038/s41598-025-02483-0

Scopus: View on Scopus

PubMed: 40394185

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Rashdan H.R.M., Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Buhouth St, Dokki, Giza, 12622, Egypt; Hassan S., Electron Microscopy Department, Theodor Bilharz Research Institute, Giza, Egypt; Maher S., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Okasha H., Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Liver necrosis is the irreversible loss of hepatocytes through toxin-induced injury, ischemia, or infection to produce organ dysfunction. It is a significant pathological marker in many liver disorders, including cirrhosis, and hepatitis, and contributes to organ failure and general systemic effects. This research aims to evaluate the protective effects of a newly synthesized compound named 1-(5-((1-(1-(4-((4-(4-(1-((5-acetyl-3-phenyl-1,3,4-thiadiazol-2(3H)-ylidene)hydrazono)ethyl)-5-methyl-1H-1,2,3-triazol-1-yl)phenyl)sulfonyl)phenyl)-5-methyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-4-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one (TTTE) sulfone-bis chalcone derivative on liver necrosis caused by TAA therapy using murine model. The research investigates optimal cellular pathways which demonstrate the therapeutic properties of TTTE as a potential treatment for liver injuries. The newly prepared compound TTTE was successfully characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) spectroscopy, carbon-13 nuclear magnetic resonance (13C-NMR), The safety of the as-prepared compound TTTE was determined based on weight changes and the behaviors in all the groups were monitored for 21 days. The effect of treatment of TTTE at different doses (300, 200, and 100 mg/kg B.W.) was studied. High-dose TTTE revealed a 62.5% survival rate compared to the untreated TAA group (40%). Molecular analysis exhibited that high-dose TTTE downregulated Cas-3, TIMP-1, and proinflammatory cytokines (TNF-α, NF-κB, and IL-6) compared to untreated TAA. Results of histopathological and IHC examinations exhibited high TTTE dose have no signs of liver injury with suppression in TGF-β expression as a result of anti-inflammatory response. Our study concluded that the synthesized compound, TTTE has a potential therapeutic strategy in mitigating liver necrosis. © The Author(s) 2025.

Keywords

Apoptosis; Inflammation; Liver necrosis; Sulfone bis-compound; TAA; Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Drug Design; Liver; Male; Mice; Necrosis; Sulfones; Thioacetamide; sulfone; animal; chemistry; disease model; drug effect; drug therapy; metabolism; mouse; pathology; synthesis

Citation Information

Scopus Citations: 1

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