The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones.
This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a-c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC(50) values in the two series of compounds are presented based on molecular modeling, logP values and respiration in rat liver mitochondria.
Pati
Hari N
HN
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Das
Umashankar
U
Das
Swagatika
S
Bandy
Brian
B
De Clercq
Erik
E
Balzarini
Jan
J
Kawase
Masami
M
Sakagami
Hiroshi
H
Quail
J Wilson
JW
Stables
James P
JP
Dimmock
Jonathan R
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007659:Ketones; D010881:Piperidones; C017582:3-octanone