title: Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo toxicity study of substituted N,N'-bis(arylmethyl)benzimidazolium salts against a panel of non-small cell lung cancer cell lines.
abstract: A series of N,N'-bis(arylmethyl)benzimidazolium salts have been synthesized and evaluated for their in vitro anti-cancer activity against select non-small cell lung cancer cell lines to create a structure activity relationship profile. The results indicate that hydrophobic substituents on the salts increase the overall anti-proliferative activity. Our data confirms that naphthylmethyl substituents at the nitrogen atoms (N1(N3)) and highly lipophilic substituents at the carbon atoms (C2and C5(C6)) can generate benzimidazolium salts with anti-proliferative activity that is comparable to that of cisplatin. The National Cancer Institute's Developmental Therapeutics Program tested 1, 3-5, 10, 11, 13-18, 20-25, and 28-30 in their 60 human tumor cell line screen. Results were supportive of data observed in our lab. Compounds with hydrophobic substituents have higher anti-cancer activity than compounds with hydrophilic substituents.
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Shelton
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: DeBord
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Wagers
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Marie R
authors.initials: MR
authors.lastname: Southerland
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Travis M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Nikki K
authors.initials: NK
authors.lastname: Robishaw
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Tessier
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA. Electronic address: youngs@uakron.edu.
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D002945:Cisplatin
keywords: Anti-cancer; Anti-proliferative; Anti-tumor; Benzimidazolium salt; Lung cancer