Synthesis, Raman, FT-IR, NMR spectroscopic characterization, antimicrobial activity, cytotoxicity and DNA binding of new mixed aza-oxo-thia macrocyclic compounds

• Published in: European journal of medicinal chemistry 2009-11, Vol.44 (11), p.4681-4689
• Main Authors: Aghatabay, Naz M., Baş, A., Kircali, A., Şen, G., Yazicioğlu, M.B., Gücin, F., Dülger, B.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Apoptosis - drug effects; Apoptotic; Bacteria - drug effects; Biological and medical sciences; Cattle; Cell Line, Tumor; CT-DNA; Cytotoxic; DNA - metabolism; FT-Raman; General aspects; Humans; Inhibitory; Macrocyclic; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - pharmacology; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Yeast cultures; Yeasts - drug effects
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.07.003

Series of new mixed aza-oxo-thia macrocyclic ligands 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithia-cyclohexadecaphan-1 4,9 4-diphenyl ( L 1 ); 1,10(2,6)-ditri azina-2,9,11,18-tetraaza-3,8,12,17-tetraoxo-5,6,14,15-tetrathia-cyclooctadecaphan-1 4,10 4-diphenyl ( L 2 ); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithia-cyclocosa-phan-1 4,11 4-diphenyl ( L 3 ); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathia-cyclodocosaphan-1 4,12 4-diphenyl ( L 4 ) were synthesised. The structural features of the compounds have been studied by elemental analyses, Mass, FT-Raman, FT-IR, 1H and 13C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated using disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against several bacteria and yeast cultures. The obtained results from both methods were assessed in side-by-side comparison with commercial antibacterial and antifungal agents. In most cases, the compounds show strong antifungal activity in the comparison tests. Cytotoxic activities of the ligands against two different human cancer cell lines, stomach (23132/87) and lung (A549) were determined by MTT assay. DNA fragmentation assay tested cell lines were used to analyze the DNA ladder formation which is a characteristic of apoptotic cell death. The binding of the ligands with calf thymus DNA (CT-DNA) has also been investigated by absorption spectroscopy. The following mixed aza-oxo-thia macrocyclic ligands ( L 1 – L 4 ) were synthesised. The structural features of these compounds have been studied by elemental analyses, mass, Raman, IR, 1H and 13C NMR spectroscopy. The antimicrobial activities of the ligands were evaluated. Cytotoxic activities against two different human cancer cell lines were determined by MTT assay. DNA binding has also been investigated by absorption spectroscopy. [Display omitted]