Synthesis, antiinflammatory, and cytotoxic activities of 2-alkyl and 2-benzyl-2-dimethylaminomethyl-5-(E)-arylidene cyclopentanone hydrochlorides.
OBJECTIVE
A series of 2-substituted-2-dimethylaminomethyl-5-(E)-arylidene cyclopentanones, 4 were synthesized. The main objective of this investigation was to explore the structural parameters necessary for antiinflammatory activity in this series of compounds, while keeping cytotoxic action to a minimum.


METHODS
The target compounds were synthesized in two steps commencing with 2-alkyl-cyclopentanones. Antiinflammatory, analgesic and cytotoxic activities were determined in rats. Cytotoxic results were examined in human cell lines.


RESULTS
Eight of the eighteen synthetic substances possessed significant antiinflammatory activity and twelve showed appreciable analgesic action. Cytotoxicity was minimal or non-existent for most of the compounds. The stability of one of the compounds, 4b in both aqueous and non-aqueous media, and an amine exchange reaction with aniline were used to explain the observed antiinflammatory and cytotoxic activities.


CONCLUSIONS
Unlike monosubstituted aminomethyl groups (Mannich bases) at the 2-position of 5-arylidene-2-cyclopentanones, a second substituent at the 2-position increases stability of the Mannich base and significantly decreases cytotoxic activity. Antiinflammatory and analgesic action is retained in many of the compounds, thus strongly indicating that these desired pharmacological results can be obtained without untoward damage to cells.
Shenyang College of Pharmacy, People's Republic of China.
H
H
Chen
Z
Z
Ji
L K
LK
Wong
J F
JF
Siuda
V L
VL
Narayanan
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003517:Cyclopentanes