Cytotoxicity of Mannich bases of alpha-arylidene-beta-ketoesters and related compounds against EMT6 mammary carcinoma cells.
A number of Mannich bases 2 derived from alpha-arylidene-beta-ketoesters, some corresponding deaminated products 3, and a thiol adduct 5 were prepared. High resolution 1H NMR spectroscopy revealed that, in solution, most of the bases 2 existed principally in acyclic forms, but that all members of this series underwent some intramolecular cyclization. The compounds 2, 3 and 5 possessed activity against EMT6 mammary carcinoma cells. The Mannich bases 2a-e had the highest cytotoxicity. Topliss analysis of these compounds revealed an E4 parameter dependency, in which intramolecular cyclization was minimal. The Mannich base 2f--which existed principally in the cyclic forms 6 in deuterium oxide, the deamination products, and a thiol adduct had approximately one-sixth of the activity of 2a-e.
Dimmock
J R
JR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Erciyas
E
E
Bigam
G E
GE
Kirkpatrick
D L
DL
Duke
M M
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D004952:Esters; D007659:Ketones; D008352:Mannich Bases