Potential cancer chemopreventive activity of simple isoquinolines, 1-benzylisoquinolines, and protoberberines

Abstract Seventeen simple isoquinolines, 15 1-benzylisoquinolines, and 19 protoberberines were tested for their inhibitory activities against Epstein–Barr virus early antigen (EBV-EA) activation induced by 12- O -tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among the tested alkaloids, the inhibitory activity of all 1-benzylisoquinolines and 11 protoberberines was higher than that of β-carotene. The 1-benzylisoquinolines 19 , 21 , 22 , 29 , and 34 and protoberberines 41 , 47–49 , 51, 52 , and 55 showed potent inhibitory effects on EBV-EA induction (96–100% inhibition at 1 × 10 3 mol ratio/TPA). These alkaloids were more active than the naturally occurring alkaloids, 23 , 25 , 33 , 53 , and 54 . In addition, fifteen simple isoquinolines, eighteen 1-benzylisoquinolines and eight protoberberines were evaluated with respect to their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. Nine simple isoquinolines, ten 1-benzylisoquinolines, and four protoberberines were more potent than α-tocopherol, and four 1-benzylisoquinolines, 20 and 28 – 30 , exhibited potent activities (SC 50 4.5–5.8 μM). Their activities were higher than the naturally occurring alkaloids, 23 , 25 , and 33 . Therefore, some of the isoquinoline alkaloids indicating the high activity on both assays may be potentially valuable cancer chemopreventive agents. Structure–activity relationships are discussed for both tests.