Author/Authors :
Overhand، نويسنده , , Mark and Stuivenberg، نويسنده , , Hanneke R. and Pieterman، نويسنده , , Elsbet and Cohen، نويسنده , , Louis H. and van Leeuwen، نويسنده , , Rick E.W. and Valentijn، نويسنده , , A.Rob P.M. and Overkleeft، نويسنده , , Herman S. and van der Marel، نويسنده , , Gijs A. and van Boom، نويسنده , , Jacques H.، نويسنده ,
Abstract :
Novel diphosphonate homologs7a–7c,and their cyclic counterparts8a–8c,of the previously synthesized farnesyl pyrophosphate analogs1and2were prepared and tested for their inhibition potency and specificity of the enzymes PFT and PGGT-I. Compound2was shown to be the most potent inhibitor of PFT (IC50= 0.58 ± 0.45 μM) in this series. The novel compound7a,the one carbon homolog of2,proved to be the most potent inhibitor of PGGT-I (IC50= 0.98 ± 0.01 μM). The cyclic analogs8a–8care generally less biologically active. The compounds2and7aare nonspecific toward inhibition of PFT and PGGT-I and may inhibit both farnesylation and geranylgeranylation processing of oncogenic proteins.
