SYNTHESIS AND CYTOTOXIC EVALUATION OF SOME CYCLIC ARYLIDENE KETONES AND RELATED OXIMES, OXIME ESTERS, AND ANALOGS

A number of arylidene derivatives of alicyclic ketones and some corres ponding oximes, oxime esters, and related compounds were prepared as c andidate cytotoxic agents. All of the compounds were evaluated against murine L1210 lymphoid leukemia cells. In general, cytotoxicity was gr eatest with the alpha,beta-unsaturated ketones and diminished with the oximes, and the oxime esters had little or no activity in this screen . When the same compounds were examined in both the in vitro L1210 and P388 leukemia screens, in the majority of cases the L1210 cells were more sensitive to these derivatives. Over half of the compounds prepar ed were evaluated against approximately 55 human tumors in vitro and s howed selective toxicity toward one or more groups of neoplastic disea ses, particularly leukemia. Some correlations between structure and bi oactivity were discerned. The cytotoxicity screening and stability stu dies of representative compounds suggested that the ketones, oximes, a nd oxime esters were stable under the conditions of bioevaluation. X-r ay crystallography of four representative compounds revealed structura l features associated with cytotoxicity which may be considered in the design of future candidate cytotoxins.