Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents.
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).
Poza
Javier
J
Departamento de Química Fundamental, Facultade de Ciencias, Universidade de A Coruña, Campus da Zapateira, 15071 A Coruña, Spain.
Rega
Miriam
M
Paz
Vanessa
V
Alonso
Beatriz
B
Rodríguez
Jaime
J
Salvador
Nélida
N
Fernández
Antonio
A
Jiménez
Carlos
C
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
D003603:Cytotoxins; D004852:Epoxy Compounds; D007097:Imines; D013256:Steroids; D005461:Fluorine; D010100:Oxygen