title: Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines.
abstract: Synthesis, characterization, anticancer activity, and comparative molecular field analysis (CoMFA) of 14 argentatin B (1) analogs are described. The effect of argentatin B derivatives on the growth of K562 (leukemia), PC-3 (prostate), U251 (CNS), and HCT-15 (colon) human cancer cell lines was determined using the sulforhodamine B test. The most active compound in this series, 2-formyl-(16beta,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one (12), was about 35-50 times more potent than argentatin B (1). Structures were built using the X-ray crystallography of six derivatives for 3D modeling with Sybyl6.9. CoMFA of Log (1/IC50) in K562 cell line gave q2 = 0.507, r2 = 0.907, and three components. The standard deviation CoMFA contours indicate that increased activity is associated with a bulky group at C-2, a C1-C2 double bond, and low electronic density at C-25. Experimental Log P values for argentatin B and one derivative were 1-2 Log units more hydrophilic than the calculated CLog P values.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México, D.F., Mexico.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Parra-Delgado
authors.forename: César M
authors.initials: CM
authors.lastname: Compadre
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramírez-Apan
authors.forename: María J
authors.initials: MJ
authors.lastname: Muñoz-Fambuena
authors.forename: R Lilia
authors.initials: RL
authors.lastname: Compadre
authors.forename: Patricia
authors.initials: P
authors.lastname: Ostrosky-Wegman
authors.forename: Mariano
authors.initials: M
authors.lastname: Martínez-Vázquez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D014315:Triterpenes; C474473:argentatin B