Thiazole substituted dispiromonoansa and monospiro cyclotriphosphazenes: Design, synthesis and biological activity

Abstract

Due to their versatility, the heterocycles exist in almost all natural or synthetic organic/inorganic compounds therefore they are commonly associated with biological activity. Among the heterocycles, the cyclotriphosphazenes and thiazoles occupy a prominent position. In the present work, thiazole substituted cyclotriphosphazenes were designed, synthesized and characterized. The reactions of cyclotriphosphazene, (N3P3Cl6, 1) with spermine in chloroform yielded dispiromonoansa compound (2) and with N-Methyl-1,3-propanediamine in THF yielded monospiro compound (3). (2) and (3), then further functionalized with excess 5-hydroxy-2-methylbenzothiazole (thiazole, 4) in THF to yield disubstituted thiazole cyclotriphosphazene (5, DTC) and tetrasubstituted thiazole cyclotriphosphazene (6, TTC), respectively. Two new thiazole substituted cyclotriphosphazenes (5, 6) were fully characterized by elemental analysis, FT-IR, MALDI-TOF MS, H-1 and P-31 NMR spectroscopies. The molecular structure of DTC was also determined by X-Ray crystallography. Anticarcinogen potential of DTC was evaluated in Non-Small Cell Lung Carcinoma (NSCLC) cells which indicated a decrease in viability and increase in death of cancer cells in a concentration dependent manner.