Synthesis and cytotoxic activity of pyrazino[1,2-b]-isoquinolines, 1-(3-isoquinolyl)isoquinolines, and 6,15-iminoisoquino[3,2-b]-3-benzazocines.
A series of pyrazino[2,1-b]isoquinoline and 6,15-iminoisoquino[3,2-b]-3-benzazocine compounds related to renieramycins, cribrostatin 4, and phthalascidin was synthesized and their in vitro cytotoxic activities were evaluated against three human cancer cell lines. Pyrazino[2,1-b]isoquinolines, 6,15-iminoisoquino[3,2-b]-3-benzazocines, and other more complex octacyclic compounds have been obtained and derived to precursors of iminium ion species. Hydrogenolysis of the lactam function in pentacyclic compounds gave 1-(3-isoquinolyl)isoquinolines. The micromolar cytotoxic activity of representative structures was apparently uninfluenced by the ability to generate intermediates which would permit covalent bonding to DNA.
González
Juan Francisco
JF
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
de la Cuesta
Elena
E
Avendaño
Carmen
C
D001392:Azocines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008968:Molecular Conformation; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D001392:Azocines; D007546:Isoquinolines; D011719:Pyrazines