Potential antineoplastics. Synthesis and cytotoxicity of certain 4-chloro-3-(2-chloroethyl)-2-methylquinolines and related derivatives

In an extension of our work in the field of nitrogen heterocycles with potential cytotoxic activity, the synthesis of some substituted 4-chloro-3-(2-chloroethyl)-2-methylquinolines (10-13) from their parent 3-[1-(phenylamino)ethylidene]-dihydro-2(3H)furanones (6-9) is reported. The conversion of 10-13 to some thieno-, furo- and pyrrolo[3,2-c]quinolines (14-27, 31-33) is also described. The compounds were evaluated for their toxicity in brine shrimp (Artemia salina), and their cytotoxicity against some clinically isolated human tumors in vitro. Several compounds exhibited good toxic activity against Artemia salina, while the furanone (6, NSC 680781) displayed good antineoplastic activity and high selectivity against some cell lines from leukemia, lung cancer, colon and melanoma panels. This compound has been selected by the NCI for further testing in a new in vivo anticancer hollow fiber assay.