Synthesis and Anti-Proliferative Activity of New α-Amino Phosphonate Derivatives Bearing Heterocyclic Moiety

Condensation of 4-chloroacetophenone 1 with phenyl hydrazine 2 afforded hydrazone 3 . Further reaction of 3 with Vilsmeier reagent yielded the pyrazolaldehyde 4 in excellent yield . A one-pot, three-component reaction between aldehyde 4 , triphenylphosphite 5 , and appropriate amines in the presence of lithium perchlorate as Lewis acid catalyst gave the corresponding α-amino phosphonates 7-12(a-d) in good yields. The chemical structures of all new compounds were established by IR, 1 H NMR, and mass spectroscopy analysis. The anti-proliferative activity of the synthesized compounds against HCT-116, HepG2 and MCF-7 human cancer cells using the MTT assay was evaluated, and revealed higher anticancer activity when compared with reference drug doxorubicin. Among the tested compounds, pyrazole derivatives 4 and 9 exhibited the highest anticancer activity against breast (MCF-7), and colon (HCT-116) cancer cell lines with IC 50 = 2.7 and 3.3 μM, respectively.