| Title |
Imidazole-2-thione derivatives as new selective anticancer agents with anti-metastatic properties: synthesis and pharmacological evaluation |
| Authors |
Golcienė, Božena ; Maciejewska, Natalia ; Kallingal, Anoop ; Sapijanskaitė-Banevič, Birutė ; Stasevych, Maryna ; Mickevičius, Vytautas |
| DOI |
10.1080/14756366.2025.2607820 |
| Full Text |
|
| Is Part of |
Journal of enzyme inhibition and medicinal chemistry.. Abingdon : Taylor & Francis. 2026, vol. 41, iss. 1, art. no. 2607820, p. 1-32.. ISSN 1475-6366. eISSN 1475-6374 |
| Keywords [eng] |
anticancer ; anti-metastatic ; lung cancer ; MMPs |
| Abstract [eng] |
Imidazole scaffolds are attractive in drug design for bioactivity and synthetic accessibility. We developed S-substituted imidazole-2-thione derivatives, focusing on compound 24, which showed potent cytotoxicity against lung, cervical, and colorectal cancer cells with submicromolar IC50 and selectivity over fibroblasts. Mechanistic analyses revealed G1 arrest, caspase-dependent apoptosis, and p-γH2AX accumulation. Importantly, compound 24 strongly inhibited A-549 cell migration and invasion in both 2D and 3D assays, correlating with downregulation of MMP-2, MMP-9, and hTERT. In vitro enzyme assays further confirmed that compound 24 directly inhibits MMP-9 activity. In vivo, 24 suppressed tumour growth and vasculotropic spread in the CA M model without detectable toxicity. Docking and dynamics simulations confirmed stable binding to MMP-2 and MMP-9 active sites. These results identify compound 24 as a promising anticancer agent with both cytotoxic and anti-metastatic properties, supporting its further preclinical investigation. |
| Published |
Abingdon : Taylor & Francis |
| Type |
Journal article |
| Language |
English |
| Publication date |
2026 |
| CC license |
|
