title: Synthesis and anticancer properties of a novel bis-intercalator.
abstract: A series of naphthalene diimide (ND)-based mono-, bis-, and tris-intercalators are synthesized and evaluated for their anticancer activities. All compounds show anticancer activities in the micromolar range. Among them the bis-intercalator is the most promising. Experimental results indicate that (i) target compounds intercalate DNA and (ii) the bis-intercalator with the optimal linker shows considerably more affinity to DNA than corresponding mono-and tris-intercalators. Spectroscopic measurements indicate that the ND groups bind to the double-stranded DNA (ds-DNA) in a classical threading intercalation mode, while the cationic linker reinforces the intercalation via electrostatic interaction with ds-DNA. In vitro cytotoxicity of the bis-intercalator towards a number of cancer cells, such as C6, HeLa, and MDA-435S, is tested and compared to that of normal cells. Attractive anticancer activity is observed with the bisintercalator, which provides a new lead in the anticancer drug design strategy.
authors.affiliation: Department of Chemistry, National University of Singapore, Singapore 117543.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Huimin
authors.initials: H
authors.lastname: Deng
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007094:Imides; D009281:Naphthalenes; C542131:naphthalenediimide; D004247:DNA