| Autor: |
Selg, Christoph, Gordić, Vuk, Krajnović, Tamara, Buzharevski, Antonio, Laube, Markus, Kazimir, Aleksandr, Lönnecke, Peter, Wolniewicz, Mara, Sárosi, Menyhárt B., Schädlich, Jonas, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie |
| Zdroj: |
Scientific Reports; 12/16/2024, Vol. 14 Issue 1, p1-18, 18p |
| Abstrakt: |
In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29). The tests showed that diclofenac and the carborane-substituted oxindoles exhibited no cytotoxicity, the dichlorophenyl-substituted oxindole had moderate anti-cancer activity, while with the amidine this effect was strongly potentiated with activity mapping within low micromolar range. Compound 3 abolished the viability of selected colon cancer cell line MC38 preferentially through strong inhibition of cell division and moderate apoptosis accompanied by ROS/RNS depletion. Our findings suggest that carborane-based prodrugs could be a promising direction for new anti-cancer therapies. Inhibition assays for COX-1 and COX-2 revealed that while diclofenac had strong COX inhibition, the re-engineered carborane compounds demonstrated a varied range of anti-cancer effects, probably owing to both, COX inhibition and COX-independent pathways. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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