title: Structure--activity relationship and mode of action of N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters: novel organometallic anticancer compounds.
abstract: In this article, we report the findings of a comprehensive structure-activity relationship study of N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters, in which novel analogues were designed, synthesized, and evaluated in vitro for antiproliferative effect. Two new compounds, 2 and 16, showed potent nanomolar activity in the H1299 NSCLC cell line, with exceptional IC(50) values of 0.13 and 0.14 μM, respectively. These compounds were also found to have significant activity in the Sk-Mel-28 malignant melanoma cell line (IC(50) values of 1.10 and 1.06 μM, respectively). Studies were also conducted to elucidate the mode of action of these novel organometallic anticancer compounds. Cell cycle analysis in the H1299 cell line suggests these compounds induce apoptosis, while guanine oxidation studies confirm that 2 is capable of generating oxidative damage via a ROS-mediated mechanism.
authors.affiliation: School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.
authors.forename: Aine
authors.initials: A
authors.lastname: Mooney
authors.forename: Rachel
authors.initials: R
authors.lastname: Tiedt
authors.forename: Thamir
authors.initials: T
authors.lastname: Maghoub
authors.forename: Norma
authors.initials: N
authors.lastname: O'Donovan
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Blánaid
authors.initials: B
authors.lastname: White
authors.forename: Peter T M
authors.initials: PT
authors.lastname: Kenny
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006147:Guanine / Q000737:chemistry; D006801:Humans; D000075163:Metallocenes; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004151:Dipeptides; D004952:Esters; D005296:Ferrous Compounds; D000075163:Metallocenes; D009281:Naphthalenes; D006147:Guanine; C004998:ferrocene