title: Isoquino[4,5-bc]acridines: design, synthesis and evaluation of DNA binding, anti-tumor and DNA photo-damaging ability.
abstract: Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 microM and cleaved DNA from form I to 100% form II by 50 microM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
authors.forename: Lianpeng
authors.initials: L
authors.lastname: Tong
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Li
mesh_terms: D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D018462:Photobiology
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D007546:Isoquinolines