title: New potential anticancer agents based on the anthranilic acid scaffold: synthesis and evaluation of biological activity.
abstract: The synthesis and anticancer activity of new compounds designed on the anthranilic acid scaffold are reported. The antiproliferative activity was assayed by the National Cancer Institute in established in vitro and in vivo anticancer experimental models. Structural variations based on the flufenamic acid motif afforded a series of (hetero)aryl esters of N-(2-(trifluoromethyl)pyridin-4-yl)anthranilic acid, which showed in vitro growth inhibitory properties against human tumor cell lines in nanomolar to low micromolar concentrations. The pyridinyl ester 25 exhibited very potent in vitro antiproliferative efficacy, with a chemosensitive profile showing a number of GI(50) values at concentrations lower than 10(-7) M in the full panel of human tumor cell lines. Compound 25 was also tested in vivo as a potential anticancer agent in the hollow fiber assay and in human tumor xenografts, showing moderate inhibitory properties. Analysis of biological activities and the COMPARE procedure was utilized to support putative biochemical mechanisms implicated with the antiproliferative activity.
authors.affiliation: Dipartimento di Tossicologia, Università di Cagliari, Via Ospedale 72, Cagliari, I-09124, Italy. ccongiu@unica.it
authors.forename: Cenzo
authors.initials: C
authors.lastname: Congiu
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cocco
authors.forename: Valentina
authors.initials: V
authors.lastname: Lilliu
authors.forename: Valentina
authors.initials: V
authors.lastname: Onnis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D023041:Xenograft Model Antitumor Assays; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D062367:ortho-Aminobenzoates