Fluorobenzoyl dipeptidyl derivatives as inhibitors of the Fasciola hepatica cysteine protease cathepsin L1.

Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39.

Synthesis, structural characterisation and biological evaluation of fluorinated analogues of resveratrol.

Resveratrol is a potential chemopreventive agent and can be isolated from grape skins and other dietary sources. The Wittig reaction and the decarbonylative Heck reaction were employed to synthesise analogues of this stilbene. Fluorinated derivatives of this stilbene were synthesised maintaining the 3,4',5-substitution pattern. The hydroxyl groups were also replaced by amino groups and the biological activity evaluated. The compounds were assayed on a variety of cell lines, primarily the non-small lung carcinoma cell line DLKP-A. Analogues were evaluated alone and in combination with a known chemotherapeutic agent epirubicin.