9 research outputs found
Copper(I)/(II) or silver(I) ions towards 2-mercaptopyrimidine: An exploration of a chemical variability with possible biological implication
Direct reaction of copper(I) chloride with 2-mercaptopyrimidine (pmtH) in the presence of the triphenylphosphine (tpp) in 1:1:2 M ratio forms the mixed ligand Cu(I) complex with formula
[CuCl(tpp)2(pmtH)] (1). The dimeric {[Cu(tpp)(pmt)]2 0.5(MeOH)} (2) complex was derived from the
reaction of 1 with twofold molar amount of sodium hydroxide. However, the reaction of copper(II) sulfate
or nitrate with pmtH and tpp in 1:2:2 M ratio, unexpectedly results in the formation of the
[CuSH(tpp)2(pmtH)] (3) complex. Further studies have shown that the [Cu(tpp)2(pmt)] (4) complex is
formed by reacting copper(II) acetate with pmtH in the presence of tpp in 1:2:2 M ratio, while in the
absent of tpp, the Cu(CH3COO)2 or CuSO4 is found to oxidizes pmtH to its corresponding disulfide
(pmt)2. For comparison the mixed ligand silver(I) chloride or nitrate complexes with formula
[AgCl(tpp)2(pmtH)] (5) or [Ag(NO3)(tpp)2(pmtH)] (6) are also synthesized by reacting of the AgCl or
AgNO3 with pmtH and tpp in 1:2:2 M ratio. The complexes have been characterized by elemental analyses, m.p., vibrational spectroscopy (mid-, far-FT-IR and Raman), 1
H NMR, UV–Vis, ESI-MS, TG–DTA spectroscopic techniques and single crystal X-ray crystallography at ambient conditions. Photolysis of 1–6,
was also studied and the results showed formation of triphenylphosphine oxide. The complexes 1–6,
were used to study their influence upon the catalytic peroxidation of the linoleic acid by the enzyme
lipoxygenase (LOX) experimentally and theoretically. The binding of 1–4 with LOX was also investigated
by saturation transfer difference 1
H NMR experiments (STD
Binding Conformation of 2-Oxoamide Inhibitors to Group IVA Cytosolic Phospholipase A2 Determined by Molecular Docking Combined with Molecular Dynamics
The group IVA cytosolic phospholipase A2 (GIVA
cPLA2) plays a central role in inflammation. Long chain 2-oxoamides
constitute a class of potent GIVA cPLA2 inhibitors that exhibit potent in
vivo anti-inflammatory and analgesic activity. We have now gained
insight into the binding of 2-oxoamide inhibitors in the GIVA cPLA2
active site through a combination of molecular docking calculations
and molecular dynamics simulations. Recently, the location of the
2-oxoamide inhibitor AX007 within the active site of the GIVA cPLA2
was determined using a combination of deuterium exchange mass
spectrometry followed by molecular dynamics simulations. After the
optimization of the AX007-GIVA cPLA2 complex using the docking
algorithm Surflex-Dock, a series of additional 2-oxoamide inhibitors
have been docked in the enzyme active site. The calculated binding
affinity presents a good statistical correlation with the experimental
inhibitory activity (r
2 = 0.76, N = 11). A molecular dynamics simulation of the docking complex of the most active compound has
revealed persistent interactions of the inhibitor with the enzyme active site and proves the stability of the docking complex and
the validity of the binding suggested by the docking calculations. The combination of molecular docking calculations and
molecular dynamics simulations is useful in defining the binding of small-molecule inhibitors and provides a valuable tool for the
design of new compounds with improved inhibitory activity against GIVA cPLA2