Cyclophosphamide analogues: synthesis, spectroscopic study, and antitumor activity of diazaphosphorinanes

Some diazaphosphorinanes were synthesized and characterized by 1H, 13C, 31P NMR and IR spectroscopy and elemental analysis. The antitumor activity of cyclophosphamide (CP) and its nine analogoues with formula Open image in new window , R = OC6H5CH3-4 (1), NHC6H4S(O)2NH2-4 (2), NHC(O)NHC6H4-CH3-2 (3), NHC(O)NHC6H4-NO2-2 (4), NHC(O)NHC6H4-NO2-3 (5), NHC(O)NHC6H4-NO2-4 (6), NHC(O)C6H4-NO2-2 (7), NHC(O)C6H4-NO2-3 (8), and NHC(O)C6H4-NO2-4 (9) were evaluated by cell culture on K562 cell line using MTT cell proliferation assay. The IC50 values for CP and the compounds 1–9 were in the range of 0.140 (for 3) to 58.250 μM (for 2). It was found that compounds 3–6 are the best candidates for antitumor activity close to CP. Compound 2 containing aminosulfonamide substituent is very much less toxic among these compounds.