Study On Synthesis And Antitumor Activity Of α-aminophosphonate Derivatives Containing A Quinoline Moiety

Quinoline is an important class of heterocyclic compounds. Its derivatives were widely used in the design and screening of new drug owing to their broad spectrum of biological and pharmaceutical activities such as antitumor, antimicrobial, antituberculosis, antimalaria, antioxidant and anti-HIV, etc. α-Aminophosphonates, which are analogous to both natural and unnatural amino acids, have attracted much attention and been widely used in pharmaceuticals and agricultural fields since their considerable biological and medical activities including antitumor, antiviral, antibacterial, enzyme inhibitors and insecticidal.Based on the principle of bioactive superposition, and with phosphoryl to improve the lipophilicity of drug molecule, a series of novel α-aminophosphonate derivatives containing a quinoline moiety were designed and synthesized by introducing bioactive quinoline scaffold to α-aminophosphonate, as shown in scheme 1. One intermediate and thirty-two target compounds(4A1~4A16 and 4B1~4B16) have not been reported in literature, and all the newly synthesized compounds were determined by 1H NMR, 13 C NMR, 31 P NMR, HRMS and IR. The antitumor activities of these target compounds were first investigated against two human cancer cell lines including Eca109 and Huh7 by MTT assay. Results revealed that most of target compounds exhibited moderate to high antitumor activities against the tested cancer cell lines. Among them, compounds 4B2 and 4B4 containing methyl-substituted aniline group were found to be more active than Sunitinib against both of two cancer cell lines, with IC50 in the range of 2.259~7.460 μmol/L.