Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones.
A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett sigma values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.
Dimmock
Jonathan R
JR
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Sask., Saskatoon, Canada, S7N 5C9. dimmock@skyway.usask.ca
Padmanilayam
Maniyan P
MP
Zello
Gordon A
GA
Nienaber
Kurt H
KH
Allen
Theresa M
TM
Santos
Cheryl L
CL
De Clercq
Erik
E
Balzarini
Jan
J
Manavathu
Elias K
EK
Stables
James P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D003512:Cyclohexanones / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D003512:Cyclohexanones; D008558:Melphalan; D005472:Fluorouracil