Synthesis, cytotoxicity and apoptosis of cyclotriphosphazene compounds as anti-cancer agents

• Published in: European journal of medicinal chemistry Vol. 52; pp. 213 - 220
• Main Authors: Yıldırım, Tuba, Bilgin, Kemal, Çiftçi, Gönül Yenilmez, Eçik, Esra Tanrıverdi, Şenkuytu, Elif, Uludağ, Yıldız, Tomak, Leman, Kılıç, Adem
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.06.2012; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Bacteria - drug effects; Biological activity; Biological and medical sciences; Candida albicans - drug effects; Cell Line; Chemistry Techniques, Synthetic; Chemistry, Medicinal; Cyclotriphosphazene; Cytotoxic activity; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; Medical sciences; Microbial Sensitivity Tests; Miscellaneous; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phosphorus Compounds - chemical synthesis; Phosphorus Compounds - chemistry; Phosphorus Compounds - pharmacology; Phosphorus Compounds - toxicity; Science & Technology; Spermine derivatives; Spermine derivatives; Cyclotriphosphazene; Biological activity; Cytotoxic activity; Apoptosis; ANTIBIOTIC SUSCEPTIBILITY; SPERMINE; POLYAMINES; POLYPHOSPHAZENE; GROWTH; CONFORMATIONALLY RESTRICTED ANALOGS; CYCLOPHOSPHAZENES; DERIVATIVES; BINDING
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.03.018

In the present study, a number of new dispirobino and dispiroansa spermine derivatives of cyclotriphosphazene (8–10, 13) were synthesized and characterized by elemental analysis, mass spectrometry, 1H and 31P NMR spectroscopy. At first, in vitro cytotoxic activity of cyclotriphosphazene compounds (1–14) against HT-29 (human colon adenocarcinoma), Hep2 (Human epidermoid larynx carcinoma), and Vero (African green monkey kidney) cell lines was investigated. Our study showed that most of these compounds stimulate apoptosis and they have cytotoxic effects for HT-29 and Hep2 cells. Additionally, these compounds (1–14) were investigated for their antibacterial activity against gram-positive (Staphylococcus aureus), gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and for their antifungal activity against Candida albicans, and were shown to be inactive. Dispirobino and dispiroansa spermine derivatives of cyclotriphosphazenes. [Display omitted] ► Dispirobino and dispiroansa spermine derivatives of cyclotriphosphazene (7–11). ► The cytotoxic effects of cyclotriphosphazene compounds (MTT assay). ► Induction of apoptotic cell death in cells for cyclotriphosphazene compounds. ►Cyclotriphosphazene compounds (8–10, 13) have been characterized by 1H and 31P NMR spectroscopy.