Chemical investigation of the ethyl acetate extract of the sponge Acanthostrongylophora ingens afford one new pyrimidine-β-carboline alkaloid named acanthomine A (2), together with two known compounds annomontine (1) and 1,2,3,4-tetrahydronorharman-1-one (3). Their structures were unambiguously established on the basis of NMR spectroscopy (1H, 13C, 1H-1H COSY, HMQC and HMBC) and mass spectrometry. The isolated compounds were tested for cytotoxic activity using brine shrimp bioassay and different cancer cell lines.