SERS Monitoring of MOlecular Interfactions Within the Supramolecular Complexes: Impact in the Design and Screenong of New Anticancer Compounds

摘要

DNA toposionmerae I (top 1) is an intracellular enzyme involved in the relaxation of DNA during the processes of DNA replication, transcriptio and repair. Human top wad identified as a cellular target for anticancer drugs~(1). Top 1 inhibitors can be grouped into two clases: topl posions and topl suppressors. The bewst characterized topl poisons are camptothecin (CPT) or some of the benzo(c)phenantridines (e.g., fagaronin) which kill cancer cells by trapping so-called cleavage complexes between topl and DNA. The typical DNA binders, including DNA intercalators (doxorubicin, aclacinomycin, etc) and minor groove binders (netropsins and bis-netropsins, polyamines, distamycin; Hoechst33258, etc0 can suppress topl-linked DNA breaks due to prevention of enzymer's access to the DNA and/or distortion of the DNA structure. The selectivity of the existing topl suppressors remains questionable. Sensitivity to topl poisons increases with topl overexpression, whereas the opposite should questionable. Sensitivity to topl poilons increases with topl overexpression, whereeas the opposite should be expected for topl suppressors~(1).