Synthesis, antitumor and antitubercular evaluation of certain new xanthenone and acridinone analogs

6-Chloro-4-substituted methyl-4-xanthenones and 2,4-dichloro-1-substituted amino-9-(10 H)-acridinones were synthesized as tricyclic planar analogs and tested for their in vitro antitumor and antitubercular activity. The obtai ned derivatives were also evaluated for two biochemical, mechanism-based sc reens to explore their ability to inhibit the cell cycle control proteins c dc2 kinase and cdc25 phosphatase as molecular targets which may account for their antitumor activity. 4-(N-1-Amidino)-sulphanilamidomethyl-6-chloro-9- xanthenone (10) proved to be the most active member of these derivatives ex hibiting a broad spectrum antitumor potency against a wide range of human t umor cell lines with full panel median growth inhibition (GI(50)), total gr owth inhibition (TGI) and median lethal concentration (LC50) mean graph mid point (MG-MID) values of 3.2, 12.7 and 21.8 mu mol l(-1), respectively. Mea nwhile, com pound 4-(N-1-Acetyl)sulphanilamidomethyl-6-chloro-9-xanthenone (9) showed GI(50), and TGI (MG-MID) values of 25.6 and 87.6 mu mol l(-1), r espectively with a moderate selectivity for leukemia cell lines at the GI(5 0) level. Compound 9 exhibited a weak in vivo growth inhibitory effect agai nst many human tumor cells cultivated in hollow fibers and implanted into t he intraperitoneal or subcutaneous physiologic compartments in mice. In add ition, compounds 15, 20, 23-25 showed potential activity against mycobacter ium strain H37Rv at 12.5 mu g ml(-1) concentration. The detailed synthesis, spectroscopic and biological data are reported.