Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity

• Published in: Molecules (Basel, Switzerland) Switzerland), 2012-09, Vol.17 (9), p.11010-11025
• Main Authors: Benci, Krešimir, Mandić, Leo, Suhina, Tomislav, Sedić, Mirela, Klobučar, Marko, Kraljević Pavelić, Sandra, Pavelić, Krešimir, Wittine, Karlo, Mintas, Mladen
• Format: Article
• Language: English
• Subjects: 1,2,4-triazole; 4,5-dicyanoimidazole and purine coumarin derivatives; acyclic nucleoside analogues; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor activity evaluation; Breast cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Coumarins - chemistry; Coumarins - pharmacology; Cytotoxicity; Drug Screening Assays, Antitumor; Estrogens; HeLa Cells; Hep G2 Cells; Humans; Imidazoles - chemistry; MCF-7 Cells; Molecular Structure; Neoplasms - drug therapy; Nucleosides - chemistry; Purines - chemistry; Structure-Activity Relationship; Triazoles - chemistry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules170911010

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their (1)H- and (13)C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC(50) = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC(50) = 33 µM), HepG2 (IC(50) = 25 µM) and SW620 (IC(50) = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.