Synthesis, Structural Analyses, Antimicrobial Activities, DNA Topoisomerase Inhibition, Cytotoxicity, and Genotoxicity Studies of Unsymmetrical Dispiro(N/N)Cyclotriphosphazenes
ChemistrySelect, cilt.11, sa.38, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 11 Sayı: 38
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/slct.74742
- Dergi Adı: ChemistrySelect
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: cytotoxicity, dispirophosphazenes, genotoxicity, spectroscopy, topoisomerase I inhibition
- Gazi Üniversitesi Adresli: Evet
Özet
In this study, the synthesis, characterization, chiral properties, and bioactivities of partially and fully substituted unsymmetrical cis-(1a-4a, S1a, S3a, and S4a) and trans-(1a-4a)dispirocyclotriphosphazenes were investigated. All cis- and trans-dispirocyclotriphosphazenes are expected to exist as pseudomesoracemates and racemates, respectively. The single-crystal X-ray analysis of trans-1a proves that the compound exists as a racemic mixture (RR'/SS'). Moreover, cis-2a is a pseudomesoracemate, and the absolute configuration of one enantiomer was found to be SR'. 31P NMR spectra of cis/trans-2a recorded with the addition of (R)-(-)-1-(9’-anthryl)-2,2,2-trifluoroethanol (CSA) confirmed these findings. Furthermore, the antimicrobial activities, DNA interactions, topoisomerase I (Topo I) inhibitory properties, cytotoxic, genotoxic and mutagenic potentials of the dispirocyclotriphosphazenes have also been demonstrated. Compounds trans-2a, cis-3b, and trans-3b show lower MBC values against Klebsiella pneumoniae ATCC 13883 than ampicillin. Cis-2a and trans-3b (MBC = 78.1 µM) are as effective as the control ketoconazole against the yeasts Candida krusei and Candida tropicalis. Since selectivity indices ranged from 0.9 to 1.8, trans-3a, trans-3b, trans-4a, and trans-4b showed moderate cytotoxic effects against HT29 human cancer cells. DNA-binding and topoisomerase-inhibition assays indicate that these effects occur through DNA binding and alteration of the compounds' topology. Trans-3b showed the highest genotoxic effect against both cancer and healthy cells.