Bioactivity, free radical scavenging properties, hCA I and hCA II esterase activities of tetraamino-(9-ethyl-3-carbazolyl)-(NN)-spirocyclotriphosphazenes: Synthesis, characterization, and structure–activity relationship (SAR) studies

Akbaş H., OKUMUŞ A., Kılıç Z., Hökelek T., SABAH B. N., AÇIK L., ...Daha Fazla

Chemical Papers, cilt.79, sa.10, ss.7211-7233, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 79 Sayı: 10
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s11696-025-04259-2
  • Dergi Adı: Chemical Papers
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Sayfa Sayıları: ss.7211-7233
  • Anahtar Kelimeler: Antioxidant, Bioactivity, hCA I and hCA II activity, Spirocyclotriphosphazene, Synthesis
  • Gazi Üniversitesi Adresli: Evet

Özet

In this study, hexachlorocyclotriphosphazene (HCCP) was reacted with diamines (9-ethyl-N-methyl-3-carbazolyl-1,2-diaminoethane, 9-ethyl-N-ethyl-3-carbazolyl-1,2-diaminoethane, and 9-ethyl-N-methyl-3-carbazolyl-1,3-diaminopropane) to synthesize the precursor compounds tetrachloro-(9-ethyl-3-carbazolyl)-(NN)-spiro-cyclotriphosphazenes, (N3P3)[(CzSpiro-n)R]Cl4. In these compounds, Cz refers to 9-ethyl carbazolyl, R represents the substituent group (Me or Et), and n denotes the chain length {n = 5 for R = –CH3 (1), n = 5 for R = –CH2CH3 (2), and n = 6 for R = –CH3 (3)}. Tetraamino-(9-ethyl-3-carbazolyl)-(NN)-spirocyclotriphosphazenes (1a-3a, 1b-3b, 1c-3c, and 1d-3d) were prepared by the replecament reactions of compounds 1–3 with pyrrolidine, piperidine, morpholine, and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The structures of carbazolyl-(NN)-spirocyclotriphosphazenes were evaulated using microanalysis, HRMS, FT-IR, as well as 1H–, 13C– and 31P-NMR spectroscopies. The crystal structure of 3b was determined by crystallographically. Moreover, the highest free radical scavenging activities (FRSAs, %) have been observed for 3a (94.4 ± 0.8), 2c (94.8 ± 0.3), and 2d (85.9 ± 0.4). Compounds 1a–3a and 1b–3b demonstrated significantly greater activity against fungi and certain G(+)-bacteria compared to standard antibiotics. Besides, the structure–activity relationship (SAR) of cyclotriphosphazenes for antimicrobial activity was evaluated. On the other hand, 1a and 2a showed higher toxicity against HT-29 (colon adenocarcinoma) cells. Additionally, the effects of all spirocyclotriphosphazenes against hCA I and hCA II (hCAs) were assessed by measuring their in vitro esterase activity. According to AC50 values, 3b appears to be the most potent activator against hCAs. However, considering both the isoform selectivities and activator potentials of the compounds, it can be suggested that 3a is the most effective hCA II activator.