title: A QSAR study on the cytotoxicity of podophyllotoxin analogues against various cancer cell lines.
abstract: The powerful inhibitory activity of podophyllotoxin (a natural product) on cell growth led to the development of clinically useful anticancer agents such as etoposide, teniposide, and etopophos. Although, these podophyllotoxin derivatives show good clinical effects against various cancers, its use often results in various undesired side effects, drug resistance, and cytotoxicity towards the normal cells. In order to overcome these limitations, it is essential to search new podophyllotoxin analogues with improved anticancer activity and fewer side effects to gain the maximum benefits for the cancer patients. With this purpose, the cytotoxicity data of two series of podophyllotoxin derivatives against four different cancer cell lines was used to develop 4 QSAR models. Hydrophobic property of the molecules was found one of the most important determining factors for their activity. The developed QSAR models showed a good correlative and predictive abilities having r(2) = 0.960 to 0.836 and q(2) = 0.911 to 0.705. On the basis of QSAR 1, two compounds (10-10 and 10-11) are suggested as potential synthetic targets. Statistical diagnostics and internal validation (cross validation and Y-randomization) tests have validated all the QSAR models. These QSAR models could be useful in the rational design of potential drug molecules with an enhanced inhibitory potency.
authors.affiliation: Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, California 91711, USA. rverma@pomona.edu
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Verma
authors.forename: Corwin
authors.initials: C
authors.lastname: Hansch
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism
chemical_list: D011034:Podophyllotoxin