title: Structure-cytotoxic activity relationships of simple hydroxylated coumarins.
abstract: Several hydroxylated and/or methoxylated coumarin derivatives were tested for their relative cytotoxicity on four human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, melanoma A-375 and promyelocytic HL-60) and three normal human cells (gingival fibroblast HGF, periodontal ligament fibroblast HPLF and pulp cell HPC). Tumor cell-specific cytotoxicity was detected in all 6,7-dihydroxy-substituted coumarins only. The observations indicate that the tumor-specific cytotoxicity of the naturally occurring coumarin esculetin can be further enhanced by proper substitutions at 3- and/or 4-position(s) of the molecule. Agarose gel electrophoresis revealed that esculetin and its derivatives with tumor-specific cytotoxicity induce internucleosomal DNA fragmentation in HL-60 cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan. kawasema@josai.ac.jp
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Ken
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Tani
authors.forename: Hermann
authors.initials: H
authors.lastname: Hauer
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chatterjee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins