Synthesis, structural characterization, DNA-binding and antimicrobial activities of series of new macrocyclic ligands and their transition metal complexes

Abstract

Aza-okso-tiya makrosiklik ligantlardan yeni iki seri; 1,7(2,6)-ditriazina-2,6,8,12-tetraaza-3,5,9,11-tetraoksosiklododekafan-14,74-dimetil (L1); 1,8(2,6)-ditriazina-2,7,9,14-tetraaza-3,6,10,13-tetraoksosiklotetradekafan-14,84-dimetil (L2); 1,9(2,6)-ditriazina-2,8,10, 16-tetraaza-3,7,11,15-tetraoksosiklohekzadekafan-14,94-dimetil (L3); 1,10(2,6)-ditriazina-2,9,11,18-tetra aza-3,8,12,17-tetraoksosiklooktadekafan-14,104-dimetil (L4); 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraokso-5,13-ditiyasiklohekzadekafan-14,94-difenil (L5); 1,10(2,6)-ditriazina-2,9,11,18-tetraaza-3,8,12,17-tetraokso-5,6,14,15-tetratiyasiklo-oktadekafan-14,104-difenil (L6); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetra-okso-6,16-ditiyasiklo-kozafan-14,114-difenil (L7); 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraokso-6,7,17,18-tetratiyasiklodokozafan-14,124-difenil (L8); ve makrosiklik olmayan 1,2-Di(o-aminofeniltiyo)etan (L9) ligandı sentezlendi. (L9) ligandının PdX2 (X = Cl, Br, I) ile olan monometalik kompleksleri hazırlandı. Ligantlar ve kompleksler elemental analiz, iletkenlik ölçümleri, FT-Raman, FT-IR, 1H and 13C NMR spektroskopi yöntemleri kullanılarak yapısal olarak karakterize edildi. Antimikrobiyal ve antifungal aktiviteleri birçok bakteri ve mantar kültürüne karşı disk difüzyon ve minimum inhibisyon konsantrasyonu (MIC) metotları kullanılarak tayin edildi. Disk difüzyon metodundan elde edilen sonuçlar bilinen antibakteriyellerden Penicilin-G, Amficilin, Cefotaxime, Vancomycin, Oflaxacin ve Tetracyclin ile tek tek karşılaştırıldı. Minumum inhibisyon konsantrasyon metodundan elde edilen sonuçlar antibakteriyel olarak Gentamycin ve antifungal olarak Nystatin ile karşılaştırıldı. Antifungal aktiviteler Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, ve Hanseniaspora guilliermondii olarak adlandırılan beş mantar kültürü üzerinde çalışılarak rapor edildi, sonuçlar ticari antifungallardan Nystatin, Ketaconazole ve Clotrimazole referans alınarak elde edildi. Ayrıca, sentezlenen ligantların DNA ile olabilecek etkileşimleri UV-görünür spektroskopi, poliakrilamit jel elektroforesis ve polimeraz zincir reaksiyonu metotları ile incelendi. Sentezlenen ligantların sitotoksisite aktiviteleri HeLa (serviks adeno karsinoma hücresi) kanser hücrelerinde araştırıldı.

Two series of novel mixed aza-oxo-thia macrocyclic ligands; 1,7(2,6)-ditriazina-2,6,8,12-tetraaza-3,5,9,11-tetraoxocyclododecaphan-14,74-dimethyl (L1); 1,8(2,6)-ditriazina -2,7,9,14-tetraaza-3,6,10,13-tetraoxocyclotetradecaphan-14,84- dimethyl (L2); 1,9(2,6)-di-triazina-2,8,10,16-tetra-aza-3,7,11,15-tetraoxocyclohexadecaphan-14,94-dimethyl (L3); 1,10(2,6)-ditriazina-2,9,11,18-tetraaza-3,8,12,17-tetraoxocyclooctadecaphan-14,104-dimethyl (L4); 1,9(2,6)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxo-5,13-dithiacyclo-hexadecaphan-14,94-diphenyl (L5); 1,10(2,6)-ditriazina-2,9,11,18-tetraaza-3,8,12,17-tetra-oxo-5,6,14,15-tetrathiacyclooctadecaphan-14,104-diphenyl (L6); 1,11(2,6)-ditriazina-2,10,12,20-tetraaza-3,9,13,19-tetraoxo-6,16-dithiacyclocosaphan-14,114-diphenyl (L7) ; 1,12(2,6)-ditriazina-2,11,13,22-tetraaza-3,10,14,21-tetraoxo-6,7,17,18-tetrathiacyclodo-cosaphan-14,124-diphenyl (L8); 1,2-Di(o-aminophenylthio)ethane (L9) and monometallic complexes of (L9) ligand with palladium halides PdX2 (X = Cl, Br, I) were synthesized. The structural features of the compounds have been investigated by elemental analyses, conductivity measurements, 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 those of Penicillin-G, Ampicilin, Cefotaxime, Vancomycin, Oflaxacin, Tetracyclin well-known antibacterial agents. The results from dilution procedure were compared with Gentamycin as antibacterial and Nystatin as antifungal. In most cases, the compounds show strong antifungal activity in the comparison tests. The binding of the ligands to genomic DNA was assessed by monitoring the change in absorption spectra at 260 nm in the presence or absence of genomic DNA. The binding ability of compounds to DNA was also determined by electrophoretic mobility shift using polyacrylamide gel electrophoresis assay (PAGE). The effect of ligands on Taq polymerase-catalyzed gene amplification reaction was investigated by using PCR method. The cytotoxicity assay was performed using human cervical cancer HeLa cells.