Synthesis and in vitro antitumor activity of β-carboline hybrid imidazole derivatives
A series of β-carboline hybrid imidazole compounds were synthesized from L-tryptophan by Pictet-Spengler cyclization,oxidative decarboxylation and N9-alkylation,and then characterized by 1HNMR,13CNMR and HRMS.The in vitro antitumor activities of β-carboline hybrid imidazole derivatives against five cancer cell lines of lung cancer cells(A-549),stomach cancer cells(BGC-823),colon cancer cells(CT-26),liver cancer cells(Bel-7402),and breast cancer cells(MCF-7)were evaluated using thiazolylblue(MTT)method.The results showed that most of the compounds exhibited moderate to excellent activity against the tested cancer cell lines.Especially,3-benzyl-11-(3-phenylpropyl)-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴr)showed the most potent anti-proliferative activity against CT-26,Bel-7402,and MCF-7 cell lines with corresponding median inhibitory concentration(IC50)of(9.5±0.4),(7.4±0.3),and(8.8±0.6)µmol/L,respectively.Molecular docking results revealed that 3-benzyl-11-methyl-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴa),3-benzyl-11-butyl-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴf),andⅤr had a good binding effect on several amino acid residues of VEGFR2 enzyme.