Peptidomimetic 2-cyanopyrrolidines as potent selective cathepsin L inhibitors |
| |
Authors: | Yadav Mange R Shinde Anil K Chouhan Bishram S Giridhar Rajani Menard Robert |
| |
Institution: | Pharmacy Department, Faculty of Technology and Engineering, The M S University of Baroda, Vadodara, India. mryadav11@yahoo.co.in |
| |
Abstract: | Cathepsins have been found to have important physiological roles. The implication of cathepsin L in various types of cancers is well established. In a search for selective cathepsin L inhibitors as anticancer agents, a series of 2-cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were designed. Two series of compounds, one with a benzyl moiety and a second with an isobutyl moiety at P(2) position of the enzyme were synthesized. The synthesized compounds were evaluated for inhibitory activity against human cathepsin L and cathepsin B. Although, none of the compounds showed promising inhibitory activity, (E)N-{(S)1-(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3-diphenylacrylamide (24) with an isobutyl moiety at P(2) was found to show selectivity as a cathepsin L inhibitor (Ki 5.3 microM for cathepsin L and Ki > 100 microM for cathepsin B). This compound could act as a new lead for the further development of improved inhibitors within this inhibitor type. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|