Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines and their Mannich bases.

Abstract A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines ( 4a – e ) and the corresponding Mannich bases 5 – 9 ( a – c ) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a – e series showed a broad spectrum of antitumor activity, with GI 50 values lower than 15 μM for five cell lines. The derivative 4b , having the N , N -dimethylaminophenyl group at C-1, displayed the highest activity with GI 50 in the range of 0.67–3.20 μM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines ( 5a , 5b , 6a , 6c and 9b ), and ovarian (OVCAR-03) cell lines ( 5b , 6a , 6c , 9a , 9b and 9c ). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.