ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Hüseyin Akbaş, Aytuğ Okumuş, Zeynel Kılıç, Tuncer Hökelek, Büşra Nur Sabah, Leyla Açık, Süheyla Pınar Çelik, Ekrem Tunca, Nagihan Kaya, and Ayşegül Şenocak

Faculty of Arts and Sciences, Department of Chemistry, Tokat Gaziosmanpaşa University, Tokat, Türkiye

E-mail: huseyin.akbas@gop.edu.tr

Received: 8 April 2025  Accepted: 14 July 2025

Abstract:

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.

Keywords: Spirocyclotriphosphazene; Synthesis; Bioactivity; Antioxidant; hCA I and hCA II activity

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04259-2

Chemical Papers 79 (10) 7211–7233 (2025)