Quantitative structure-cytotoxicity relationship of newly synthesized tropolones determined by a semiempirical molecular-orbital method (PM5).
A semiempirical molecular-orbital method (CONFLEX/PM5) was applied to delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic concentration, CC(50)) of twenty-four tropolone-related compounds and their molecular weight or one of the following eleven chemical descriptors: the heat of formation (COSMO, non-COSMO; kcal/mole), stability of hydration (=COSMO-nonCOSMO (DeltaH); kcal/mole), dipole moment (D), hydrophobicity (log P), highest occupied molecular orbital energy (E(HOMO); eV), lowest unoccupied molecular orbital energy (E(LUMO); eV), absolute hardness [eta=(E(LUMO)-E(HOMO))/2; eV)], absolute electron negativity [chi=-(E(LUMO)+E(HOMO))/2; eV], reactivity index (omega=chi(2)/2eta; eV), surface area (A(2)) and volume (A(3)) of the molecule. No good correlation was found with the unseparated twenty-four compounds all together, but modest to high correlation was found after separation into three different groups of compounds, depending on the structural similarity. Particular descriptors could be used to evaluate the biological activity of newly synthesized tropolones.
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
Mariko
M
Ishihara
Hidetsugu
H
Wakabayashi
Noboru
N
Motohashi
Hiroshi
H
Sakagami
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008970:Molecular Weight; D009062:Mouth Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship; D013365:Submandibular Gland Neoplasms / Q000188:drug therapy; D013816:Thermodynamics; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014334:Tropolone