title: Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents.
abstract: Taking into account the structural requirements for cytotoxicity, several new hydroximinosteroid derivatives have been prepared and evaluated for their cytotoxic activity against A-549, H116, PSN1, and T98G cultured tumor cell lines in order to obtain further information on the potential pharmacophoric core of this type of compound. The influence of the oxygenated position in the A ring, the presence of an additional oxygenated position at C-7 and C-16, and a fluorinated position at C-5 were considered in order to study the structure-activity relationships. The results reveal the importance of oxygenated positions in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under micromolar level) for an increase in cytotoxic activity in this type of compound. Furthermore, they showed an important selectivity toward colon tumor line (HCT-116).
authors.affiliation: Departamento de Química Fundamental, Facultade de Ciencias, Universidade de A Coruña, Campus da Zapateira, 15071 A Coruña, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Poza
authors.forename: Miriam
authors.initials: M
authors.lastname: Rega
authors.forename: Vanessa
authors.initials: V
authors.lastname: Paz
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alonso
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Nélida
authors.initials: N
authors.lastname: Salvador
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández
authors.forename: Carlos
authors.initials: C
authors.lastname: Jiménez
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004852:Epoxy Compounds / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D003603:Cytotoxins; D004852:Epoxy Compounds; D007097:Imines; D013256:Steroids; D005461:Fluorine; D010100:Oxygen