NAPHTHALIMIDO DERIVATIVES AS ANTIFOLATE THYMIDYLATE SYNTHASE INHIBITORS

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structural ly related to the previously reported thymidylate synthase (TS) inhibi tor naphthaleins 3, were synthesized and compounds tested for their in hibition of several species of TS. Moreover, their in vitro cytotoxici ty together with antimycotic and antibacterial properties were assayed . While no activity was detected in the antibacterial tests, the m-nit ro (4ae) and the p-nitro (4af) derivatives were found able to partiall y inhibit TS at low micromolar concentrations. Introduction of nitro o r (substituted)-amino groups in position 4 of the naphthalic ring alwa ys led to less active compounds.