title: Estimation of relationship between the structure of trihaloacetylazulene derivatives determined by a semiempirical molecular-orbital method (PM5) and their cytotoxicity.
abstract: We have previously reported the cytotoxicity and type of cell death induced by twenty trihaloacetylazulenes in human tumor cell lines. We determined for the first time the most-stable chemical structures from their reported structures, using the semiempirical molecular-orbital method (CONFLEX/PM5), and then delineated the relationship between their cytotoxicity (evaluated by 50% cytotoxic concentration, CC(50)) and a total of twelve parameters. The parameters used are the molecular weight and eleven chemical descriptors: the heat of formation (COSMO, non-COSMO), stability of hydration (=COSMO - nonCOSMO (DeltaH)), dipole moment (D), hydrophobicity (log P), highest occupied molecular orbital energy (E(HOMO)), lowest unoccupied molecular orbital energy (E(LUMO)), absolute hardness [eta=(E(LUMO)-E(HOMO))/2], absolute electron negativity [chi=-(E(LUMO)+E(HOMO))/2], reactivity index (omega=chi(2)/2eta) and surface area (A(2)), and volume of the molecule (A(3)). There was good correlation between the CC(50) value and all descriptors except for absolute hardness in HL-60 cells. There was also a good correlation between the CC(50) value and EHOMO, chi, omega, surface area, volume and molecular weight in HSC-2, HSC-3 and HSC-4 cells. The descriptors determined by the present method are useful in evaluating the biological activity of trihaloacetylazulenes.
authors.affiliation: Division of Basic Chemistry, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. mariko@dent.meikai.ac.jp
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: Noboru
authors.initials: N
authors.lastname: Motohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D052176:Azulenes / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018922:HL-60 Cells; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052176:Azulenes