Preparation and cytotoxicity toward cancer cells of mono(arylinaino) derivatives of beta-lapachone

A regio- and stereospecific synthesis of monoarylimino o-quinones derived f rom beta -lapachone (1) was achieved by treatment of the quinone with a sli ght excess of an arylamine in the presence of an excess of triethylamine/ti tanium tetrachloride 4:1. Imine formation occurred exclusively at position 6, giving the Z diastereomer, as determined by single-crystal X-ray analysi s. In vitro tests for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in activity for the p-nitrophenylimine (5), whereas the phenylimine (2), p-methylphenylimine (3), and p-methoxyphenylimine (4) reta ined (or bettered) most of the cytotoxicity and selectivity of the parent q uinone. Preliminary in vivo testing in hollow fiber assays against a standa rd panel of 12 human tumor cell lines showed that although beta -lapachone failed, compounds 2 and 3 had good scores with net cell kills.