Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

“…By this method, 22 new arylthiophenes 1 were obtained in sufficient amount to evaluate their activity on protein farnesyltransferase. We previously observed that the ester forms of our FTIs were more active on parasites than their acidic forms 34 . Therefore, to evaluate the antiparasitic activity of our series, we synthesized the corresponding esters of the selected active thiophene 2-carboxylic acids 1j, 1aa and 1gg (see below), according to Scheme 2.…”

Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling

“…In addition, new imidazole-containing derivatives linked by an acidic substituent and a peptidyl chain were also synthesized as bisubstrate FTIs, and the designed bisubstrate inhibitors have better affinities than FPP [59]. The FTIs in the second class are peptidomimetic molecules, which can be divided into two groups, namely thiol and non-thiol FTIs.…”

“…The representative FTIs roughly belong to two classes ( [59]. In addition, new imidazole-containing derivatives linked by an acidic substituent and a peptidyl chain were also synthesized as bisubstrate FTIs, and the designed bisubstrate inhibitors have better affinities than FPP [59].…”

An Accurate Metalloprotein-Specific Scoring Function and Molecular Docking Program Devised by a Dynamic Sampling and Iteration Optimization Strategy

“…The energy terms used in eq 3 are given by eqs 4−6 and are designed as the objective functions f 1 (x)−f 3 (x) of the multiobjective optimization model of MpSDock Zn : (6) where E k,j,AMBER vdW (r) and E k,j,AMBER es (r) in eq 4 are the vdW and electrostatic interactions, respectively, between protein atom k and ligand atom j at a distance r as evaluated using the AMBER ff99SB force field; E Zn,j,SLEF es (r) and E Zn,j,SLEF vdW (r) in eq 5 are the vdW and electrostatic interactions between the zinc ion and ligand atom j at a distance r as defined by the SLEF force field; and E i,l,AMBER vdW (r) and E i,l,AMBER es (r) in eq 6 represent the internal vdW and electrostatic interactions of the nonbonded atom pair i, l of the ligand at a distance r as evaluated using the AMBER ff99SB force field.…”