3,5-Bis-arylidene-1-methyl-4-piperidone methohalides and related compounds with activity against L 1210 cells and DNA binding properties.
A series of 3,5-bis-arylidene-1-methyl-4-piperidone methohalides 2 and two related analogues in general demonstrated activity against L 1210 leukemia cells in vitro and bound to a synthetic DNA, poly[d(AT)]. Plots of various physicochemical constants of the aromatic substituents in series 2 versus the IC50 figures revealed correlations between the aryl MR and pi values but not the sigma constants. The delta Tm values of six members of series 2 were correlated with the MR figures of the aryl substituents but not the sigma nor pi values of the aromatic atoms and groups. Some suggestions for future molecular modification with a view to increasing cytotoxicity are presented.
Dimmock
J R
JR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Arora
V K
VK
Semple
H A
HA
Lee
J S
JS
Allen
T M
TM
Kao
G Y
GY
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism*; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D004273:DNA, Neoplasm; D010881:Piperidones; D011728:Pyridones