Synthesis of Dihydrothiophene Ureidoformamide Derivatives and Exploration of Their Potential Anticancer Activity.

Khawla Boudebbous, Arif Mermer, Tuğba Kul Köprülü, Dominique Harakat, Anthony Robert, Anthony Abou Dib, Houssem Boulebd

Journal: Journal of biochemical and molecular toxicology 2026;40(7):e70994

PMID: 42371741

Abstract

Dihydrothiophene ureidoformamide derivatives are sulfur-containing heterocyclic frameworks that remain relatively underexplored for their anticancer potential, despite possessing structural features that may enable interactions with biological targets involved in tumor progression. In the present study, a series of these derivatives was synthesized, structurally characterized, and evaluated for their anticancer activity against HCT116 human colorectal carcinoma cells. Among the tested compounds, compound 7 exhibited notable antiproliferative activity, showing a faster reduction in cell index compared to the reference drug paclitaxel during the initial 24 h of treatment, along with a dose-dependent decrease in cell index. Flow cytometric analysis using Annexin V-FITC/PI staining revealed that compound 7 induced significant apoptotic cell death, reaching 62.89% after 24 h of treatment. Molecular docking studies further indicated favorable binding interactions of compound 7 with several cancer-related targets, including EGFR, VEGFR-2, and AKT1. Overall, the obtained results suggest that this family of compounds, particularly compound 7, may represent an interesting scaffold for further investigation in the development of anticancer agents.

Address: Laboratoire d'Obtention de Substances Thérapeutiques, Université de Constantine 1, Frères Mentouri, Campus Chaabet Ersas, Constantine, Algeria.; Laboratory of Synthesis of Molecules with Biological Interest, Department of Chemistry, Frères Mentouri Constantine University, Constantine, Algeria.; Faculty of Pharmacy, University of Health Sciences, İstanbul, Türkiye.; Experimental Medicine Application and Research Center, University of Health Sciences, İstanbul, Türkiye.; Experimental Medicine Application and Research Center, University of Health Sciences, İstanbul, Türkiye.; Department of Molecular Medicine, Hamidiye Institute of Health Sciences, University of Health Sciences, İstanbul, Türkiye.; Université de Reims Champagne Ardenne, CNRS UMR 7312, ICMR, URCATech, Reims, France.; Laboratory of Synthesis of Molecules with Biological Interest, Department of Chemistry, Frères Mentouri Constantine University, Constantine, Algeria.

DOI: 10.1002/jbt.70994

MeSH Terms: Humans, Antineoplastic Agents, Thiophenes, Molecular Docking Simulation, Apoptosis, HCT116 Cells, Formamides, Cell Proliferation, Proto-Oncogene Proteins c-akt, Vascular Endothelial Growth Factor Receptor-2, ErbB Receptors