Synthesis and in-vitro cytotoxic activity of phenyl-amino-4-(p-toluenesulfinyl)-trans-1,5-hexadiene.
A novel anticancer drug, 1-phenyl-3-phenylamino-4-(p-toluenesulfinyl-trans-1,5-hexadiene has been synthesized and found to have in-vitro cytotoxicity against P388 (LD50 = 15 micrograms/ml) and L1210 (LD50 = 19 micrograms/ml) murine leukemia cells in culture. The LD50 compared favorably with that for doxorubicin. The compound was more cytotoxic to P388 tumor cells than to normal mouse splenocytes. The compound inhibited the uptake of both tritiated thymidine (42% inhibition) and tritiated uridine (24% inhibition) after 3 h of incubation when used at 5 micrograms/ml. No effect on uptake of tritiated leucine was observed during this time period. The compound was cytotoxic to normal mouse splenocytes which had been stimulated to divide by the mitogen concanavalin A. No effect was found on normal, non-dividing splenocytes. These results suggest that this novel compound is cytotoxic to leukemic cells or other rapidly dividing cells through inhibition of DNA and/or RNA synthesis.
Montgomery
D A
DA
Department of Biochemistry, Kansas State University, Manhattan 66506.
Cunnick
J E
JE
Coulter
M J
MJ
Sinai-Zingde
G
G
Takemoto
D J
DJ
Hua
D H
DH
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000633:toxicity; D007939:Leukemia L1210 / Q000473:pathology; D007941:Leukemia P388 / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011241:Prednisone / Q000633:toxicity; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D012313:RNA / Q000096:biosynthesis; D013454:Sulfoxides / Q000138:chemical synthesis / Q000633:toxicity*
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D013454:Sulfoxides; C057310:1-phenyl-3-phenylamino-4-(4-toluenesulfinyl)-1,5-hexadiene; D012313:RNA; D004317:Doxorubicin; D004247:DNA; D011241:Prednisone