Inhibitory activity of benzo[h]quinoline and benzo[h]chromene in human glioblastoma cells

Purpose: To carry out a neat synthesis of 2-amino-5,6-dihydro-8-methoxy-4-phenylbenzo[h]quinoline-3-carbonitrile (compound 2) and 2-amino-5,6-dihydro-8-methoxy-4-phenyl-4H-benzo[h]chromene-3-carbonitrile (compound 3) and evaluate their cytotoxic activity in human glioblastoma cells.
Methods: Benzo[h]quinoline and benzo[h]chromene were synthesized by treating 6-methoxy-1-tetralone with benzylidenemalononitrile under microwave irradiation. The structures of compounds 2 and 3 were confirmed by elemental, spectral, and x-ray crystallographic analyses. The cytotoxic activity of compounds 2 and 3 was evaluated using WST-1 assay in U373 human glioblastoma cell line.
Results: The molecular structures of compounds 2 and 3 were demonstrated unambiguously from single crystal x-ray measurements and they crystallized in triclinic form, P-1, for both compounds. In-vitro cytotoxic activity data for compound 2 in human glioblastoma cell line (U373) indicate that no significant cytotoxicity was observed. On the other hand, compound 3 showed highly significant cytotoxic effects on U373 cells at concentrations starting from 0.1 μg/ mL.
Conclusion: Compound 3 produces a decrease in cell viability with approximately 80 % cell death while compound 2 did not indicate significant cytotoxic activity. This suggests that the chromene moiety of compound 3 may be responsible for its high cytotoxicity.

Keywords
Hydronaphthaline; Benzo[h]quinolone; Benzo[h]chromene; X-ray crystallography; U373 human glioblastoma; Cytotoxicity; Chromene moiety