title: 3-Arylisoquinolines as novel topoisomerase I inhibitors.
abstract: Topoisomerase I (topo I) is an essential enzyme for vital cellular processes. Inhibition of topo I activities is lethal and leads to cell death, thus establishing topo I as a promising target for cancer treatment. Camptothecin, a natural alkaloid, inhibits topo I. Topotecan and irinotecan, synthetic derivatives of camptothecin, are the most potent anticancer drugs in clinical use. However, several limitations of camptothecins such as solubility, toxicity, stability, resistance and the required high drug dose have encouraged the development of non-camptothecin topo I inhibitors. Natural alkaloid benzo[c]phenanthridines and synthetic indenoisoquinolines have been extensively studied as alternatives to camptothecin. Interestingly, these non-camptothecin topo I inhibitors share a common 3-arylisoquinoline scaffold. This review will describe the development of novel indeno[1,2-c]isoquinolines, isoindolo[2,1-b]isoquinolines, 12-oxobenzo[c]phenanthridines and benz[b]oxepines with a 3-arylisoquinoline nucleus as topo I inhibitors.
authors.affiliation: Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Daulat Bikram
authors.initials: DB
authors.lastname: Khadka
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I