7,8-dihydro-5H-isoindolo[1,2-b] [3]benzazepine-5-ones. Part 2: In vitro effect of derivatives substituted at position 7 on leukemia P 388 cells.
The in vitro cytotoxic effect on leukemia P 388 cells of new derivatives, 7,8-dihydro-5H-isoindolo[1,2-b] [3] benzazepine-5-ones substituted at position was evaluated. The most effective were the derivatives which were substituted at position 7 by the dimethylamino, hydroxy and/or ethoxy group. These substances selectively inhibited incorporation only of 14C-uridine into P 388 cells fractions. Substance 7 which was studied more intensively stopped the proliferation of P 388 cells in vitro, but caused only a slight killing effect. The maximum inhibitory effect of this substance on P 388 cells is related to the G1/S phase of the cell cycle. In in vitro test, the substance showed synergism with the cytostatics: cycloheximide, methotrexate and vermiculin, their phase of greatest lethal activity also being G1/S or early S.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004357:Drug Synergism; D066298:In Vitro Techniques; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013997:Time Factors; D014529:Uridine / Q000378:metabolism
D000970:Antineoplastic Agents; D001552:Benzazepines; D009363:Neoplasm Proteins; D014529:Uridine; D008727:Methotrexate