SYNTESIS AND ANTIINFLAMMATORY AND ANTICANCER ACTIVITIES OF 2-(E)-(UN) SUBSTITUTED BENZYLIDENE CYCLOPENTANONES AND THEIR MANNICHBASE 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, hasbeencarriedout. Inthepresent 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, Ⅱ₁₂ 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 respectivily, was similar to Ibuprofen. Some compounds of type Ⅱ exhibited anticancer activity both in vitro (IC₅₀ ranging from 2.93 to 18.06/μmol/L on L1210)and in vivo (maximum increase of life span was 97.5% on EAC in mice).