Novel tetracyclic spermine derivatives of cyclotriphosphazene: Design, synthesis and biological activity

Abstract

Lung cancer is amongst the deadliest form of cancer that categorized in two main groups as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which arises more often and typically grows at a slower rate than SCLC. Treatment limitations due to the side effects and resistance to the current therapeutics' mandates development of alternative agents. In this study, novel tetracyclic spermine derivatives of cyclotriphosphazene (6-8) were designed and synthesized and their effects were investigated in NSCLC cell lines and non-tumoral counterparts. First, the reactions of dispiroansa (tetracyclic) spermine substituted cyclotriphosphazene derivative (2) with pyrrolidine (3), piperidine (4) and cyclopropylmethanamine (5) were performed, respectively and synthesised products (6-8) were characterized by FT-IR, MALDI-TOF MS, H-1, P-31 NMR spectroscopies and single crystal X-ray (for compound 7) crystallography. Then, the anti-carcinogenic properties of compounds have been determined by viability and cell death assays. Our results indicated that compared to others, compound 8 that is formed by the substitution reaction of compounds 2 and 5 has a potential anti-cancerogenic effect on lung cancer cells. (C) 2022 Elsevier B.V. All rights reserved.