Phosphorus-nitrogen compounds: Part 31. Syntheses, structural and stereogenic properties, in vitro cytotoxic and antimicrobial activities, and DNA interactions of bicyclotetraphosphazenes containing bulky side group

Abstract

Hexachlorocyclotriphosphazene, N3P3Cl6, and octachlorocyclotetraphosphazene, N4P4Cl8, were reacted with K2N2O2 salt of symmetric tetradentate ligand to obtain spiro-bino-spiro [(sbs) (2)] and 2,6-spiro-ansa-spiro [(2,6-sas) (3)] phosphazenes, respectively. The sbs was obtained in a very poor yield, whereas, 2,6-sas was obtained in a moderate yield. The derivatives of 2,6-sas with mono-and diamines were synthesized. When the reactions were carried out, one equimolar amount of 2,6-sas with an excess pyrrolidine, piperidine, morpholine, 1,4-dioxa-8-azaspiro[4,5]decane (DASD), N-methylethane1,2-diamine, N-ethylethane-1,2-diamine and N-methylpropane-1,3-diamine, along with the fully substituted 2,6-sas-cyclotetraphosphazene derivatives (4a, 4b and 5a-7a), were prepared. However, the excess morpholine and DASD with 2,6-sas yielded the geminal bis-(4c and 4e) and tris- (4d and 4f) cyclotetraphosphazenes, respectively. The Cl replacement reaction of 2,6-sas with one equimolar amount of 7 led to the formation of partly substituted 2,6-sas (7b). The structures of the compounds were verified by elemental analyses, MS, FTIR, H-1, C-13{H-1}, P-31 NMR, HSQC, HMBC and X-ray crystallography (for 3 and 4a) techniques. All the 2,6-sas cyclotetraphosphazenes (except 3, 4a and 4b) have stereogenic P-atoms. All the compounds were screened for antibacterial and antifungal activities against bacteria and yeast strains. The interactions of the compounds with supercoiled plasmid pBR322 DNA were investigated. The evaluations for cytotoxic activity, and apoptotic and necrotic effects against A549 lung cancer and L929 fibroblast cell lines were introduced. (C) 2015 Elsevier B.V. All rights reserved.