Inhibition of mouse tumor metastasis with nojirimycin-related compounds

Abstract

The antimetastatic activity of ten compounds structurally related to nojirimycin A was examined using a pulmonary metastatic model of mouse B16 melanoma. Nojirimycin B, deoxynojirimycin, D-gluco-δ-lactam, CP3068 and CP3069 are structural analogues of nojirimycin A, and showed potent or moderate antimetastatic activities. Nojirimycin A, nojirimycin B, deoxynojirimycin and D-gluco-δ-lactam showed potent or moderate inhibitory activities against α-glucosidase, β-glucosidase and β-mannosidase, but CP3068 and CP3069 in which the structures were related to D-gluco-δ-lactam showed no inhibitory activities. CP3041, CP3042, CP3043, CP3045 and CP3048 are analogues of sodium D-glucaro-δ-lactam (ND2001), a carboxy derivative of nojirimycin A, and showed potent or moderate antimetastatic activities. But no analogue was superior to ND2001 concerning with antimetastatic and anti-β-glucuronidase activities. CP3041 and CP3042 showed potent and moderate inhibitory activities against β-glucuronidase, respectively, but CP3043, CP3045 and CP3048 showed little or no activities.