Phosphorus nitrogen compounds: Part 34. Syntheses, structural investigations, cytotoxic and biological activities of spiro-ansa-spiro and spiro-bino-spiro tetrameric phosphazene derivatives

Abstract

The reactions of N4P4Cl8 with the symmetric N2N2 (1–3) and N2O2 (4) bulky ligands gave partly substituted 2,4-sas (5 and 6), 2,6-sas (7–10) and sbs (11–14) tetrameric phosphazene derivatives. The 2,4-sas-5, 2,6-sas-8 and sbs-12 reacted with pyrrolidine to give fully-substituted tetra- (15 and 16) and dodecapyrrolidinocyclotetraphosphazenes (17–19). The structures of all the phosphazenes were verified by FTIR, MS, 1H, 13C{1H} and 31P{1H} NMR, and HSQC spectral data. The crystal structures of 7, 9 and 10 were examined by single crystal X-ray diffraction techniques. The compounds 1–3, 5, 8, 9, 12, 13, 16 and 18 were screened for antimicrobial activity against G(+) and G(−) bacteria and fungi. The compound 16 is found to possess excellent activity (MIC values of 39 and 78μM) against fungal pathogen Candida krusei and Candida albicans. Meanwhile, interactions between pBR322 plasmid DNA and 1–3, 5, 8, 9, 12, 13, 14, 16 and 18 were investigated by agarose gel electrophoresis. The compounds 5, 8, 9, 12, 13, 16 and 18 were appraised for their cytotoxic activity against L929 Fibroblast and MDA-MB-231 breast cancer cell lines. Compounds 13 and 16 are as effective as cis-platin.