Synthesis and biological evaluation of novel acylhydrazone derivatives as potential antitumor agents.
We have designed, synthesized, and evaluated as potential antitumor agents a series of 2-hydroxybenzylidene derivatives of the N-(2-trifluoromethylpiridyn-4-yl)anthranilic acid hydrazide, and some analogues bearing a (2-trifluoromethyl)piridyn-4-ylamino group in 3- or 4-position of benzohydrazide or 4-position of phenylacetohydrazide. Compounds 12e, 13e, 15e, and 16e, bearing a 4-(diethylamino)salicylidene group exhibited potent cytotoxicity, with averaged GI50 values in sub-micromolar range, and a variety of cell selectivity at nanomolar concentrations. The determination of acute toxicity in athymic nudes mice proved some compounds to be non-toxic, making them good candidates for further study as antitumor agents.
Department of Life and Environmental Sciences, Unit of Medicinal, Pharmacological and Nutraceutical Sciences, University of Cagliari, via Ospedale 72, Cagliari I-09124, Italy. Electronic address: ccongiu@unica.it.
Cenzo
C
Congiu
Valentina
V
Onnis
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D001597:Benzylidene Compounds / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D023382:Toxicity Tests, Acute; D062367:ortho-Aminobenzoates / Q000737:chemistry
D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D062367:ortho-Aminobenzoates; C031385:anthranilic acid
Acylhydrazones; Antitumor activity; Toxicity; Trifluoromethylpyridines