title: Quantitative structure-cytotoxicity relationship analysis of coumarin and its derivatives by semiempirical molecular orbital method.
abstract: A semiempirical molecular orbital method (CAChe) was applied to delineate the relationship between cytotoxicity against the human squamous cell carcinoma line HSC-2 (evaluated by 50% cytotoxic concentration, CC50) of 20 coumarin (2H-pyran-2-one) derivatives and twelve physical parameters (descriptors) calculated by the CONFLEX/PM3 method. There was a highly significant correlation between the CC50 and ionization potential, highest occupied molecular orbital (HOMO) energy, difference between electron energy of HOMO and electron energy of lowest unoccupied molecular orbital (LUMO), or absolute hardness (r2=0.756 - 0.802). On the other hand, there was no significant correlation between the CC50 and heat of formation, stability of hydration, dipole moment, electron affinity, or LUMO energy (r2=0.13.- 0.36). When the CC50 was plotted vs. log P, a parabolic curve was produced, with a maximum cytotoxicity (or the least CC50 value) at log P of 2.5. The present study demonstrated that hardness and softness, other than the electron accepting and donating properties, are important factors in estimating the cytotoxic activity of coumarin derivatives.
authors.affiliation: Division of Basic Chemistry, Department of Oral Biology and Tissue Engineering, and Meikai University School of Dentistry, Sakado, Saitama, Japan. mariko@dent.meikai.ac.jp
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yokote
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship
chemical_list: D003374:Coumarins