[Synthesis and antiinflammatory and anticancer activities of 2-(E)-(un)substituted benzylidene cyclopentanones and their Mannich base hydro chlorides].
It has been known that non-steroidal antiinflammatory drugs (NSAIDs) act by preventing cyclooxygenase products of arachidonic acid. In recent years, research on non-steroid dual inhibitors of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), which should represent a novel class of antiinflammatory drugs with a wider spectrum of activity than classical NSAIDs, has been carried out. In the present paper, a total of 29 compounds including 18 compounds of 2-(E)-(un) substituted benzylidene cyclopentanone (I) derivatives and 11 compounds of 2-(E)-(un)substituted benzylidene-5-dimethylaminomethyl cyclopentanone (II) derivatives were synthesized as dual inhibitors of CO/5-LO. Preliminary pharmacological test showed that I4, I12 and I13 given orally have significant inhibiting effect on carrageenan induced rat paw edema and most compounds of type II exhibited potent effect when given subcutaneously. In particular, II3, which inhibited by 95.8%, 70.34%, and 44.2% at 50, 25, and 12.5 mg/kg respectively, was similar to Ibuprofen. Some compounds of type II exhibited anticancer activity both in vitro (IC50 ranging from 2.93 to 18.06 mumol/L on L1210) and in vivo (maximum increase of life span was 97.5% on EAC in mice).
Chen
H T
HT
Shenyang College of Pharmacy.
Jing
Y K
YK
Ji
Z Z
ZZ
Zhang
B F
BF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D005260:Female; D007939:Leukemia L1210 / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D003517:Cyclopentanes