Estudos estruturais de duas 3 (Fenoximetil)-4-fenilbut-3-en-onas e docking no fator letal (LF) do bacillus anthracis (Antraz)
Nucci Junior, Paulo Roberto
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In this work the crystal structures of two 3 (phenoxymethyl)-4-phenylbut-3-en-ones were determined and the resulting 3D strutures were used as input for docking studies in the lethal factor (LF) of bacillus anthracis. The results were then compared with those of a known inhibitor.(3E)-3-(4-nitrophenoxymethyl)-4- phenylbut-3-en-2-one (1): the conformation about the C═C double bond [1.348 (2) Å] is E with the ketone group almost co-planar [C C C C torsion angle = 7.2 (2)°] but the phenyl group twisted away [C C C C =160.93 (17)°]. The terminal aromatic rings are almost perpendicular to each other [dihedral angle = 81.61 (9)°] giving themolecule an overall U-shape. The crystal packing feature benzene-C H O (aldehyde) contacts that lead to supramolecular helical chains along the b axis. These are connected by π π interactions between benzene and phenyl rings [inter-centroid distance = 3.6648 (14) Å] resulting in the formation of a supramolecular layer in the bc plane.(3E)-3-(2,4-dinitrophenoxymethyl)-4-phenylbut- 3-en-2-one (2): the conformation about the C=C double bond [1.345 (2) Å] is E, with the ketonemoiety almost coplanar [C C C C torsion angle = 9.5(2) °] along with the phenyl ring [C C C C = 5.9 (2) °]. The aromatic rings are almost perpendicular to each other [dihedral angle = 86.66 (7) °]. The 4-nitro moiety is approximately coplanar with the benzene ring to which it is attached [O N C C = 4.2 (2) °], whereas the one in the ortho position is twisted [O N C C = 138.28 (13) °]. The molecules associate via C H O interactions, involving both O atoms from the 2-nitro group, to form a helical supramolecular chain along . Nitro nitro N O interactions [2.8461 (19) Å] connect the chains into layers that stack along. The docking results, using as a target the lethal factor (LF) of bacillus anthracis, show that both Compound 1 and 2 located themselves in the same cavity where the known inhibitor is located, and making most of the interactions this last one does with the amino acid residues that are important for the enzyme activity, so that it can be postulated that they can be also inhibitors. Moreover, Compound 1adopts a pose closer to that of the inhibitor whereas Compound 2 is rotated so that an important interaction is missed, this may indicate that this last one can be a less effective inhibitor than Compound 1.