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The interaction of three potent antifilarial compounds (4C, 4F, and 3F) with filarial proteins thioredoxin, glutathione s-transferase and cyclophilin were investigated using molecular docking and density functional theory (DFT) studies. Molecular docking was performed using YASARA tool, Hex 8.0.0 Cuda tool and PatchDock server and docked complex were visualized by Discovery Studio 3.0. The predicted binding energy of antifilarial compounds 4C (−247.6, −243.8, −256.8 kcal mol−1), 4F (−242.6, −246.4, −232.4 kcal mol−1) and 3F (−272.4, −248.5, −277.7 kcal mol−1) with filarial protein 4FYU, 5D73, and 1A33, respectively. Docking results were strongly supported by molecular dynamics data and molecular mechanics-generalized born surface area (MM-GBSA) calculations. The optimized geometries of all three compounds were used for calculating the energies of the frontier molecular orbitals highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). The lowest HOMO–LUMO energy gap in compound 3F suggested that it is the most bioactive molecule among all these three compounds, which is in accordance with the docking results of these compounds. The interaction energies between ligand and protein are mainly due to hydrogen bonds, hydrophobic interactions, and van der Waals interactions which give the stability to the complex. The structural information and docking studies of different filarial proteins with antifilarials obtained from this study could aid in screening and designing new antifilarial or selective inhibitors for chemotherapy against filariasis. [ABSTRACT FROM AUTHOR]

The (4-acetylphenyl)amino 2,2-dimethylpropanoate ( 1) and (E)-1-(4-aminophenyl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one ( 2), were synthesized and characterized by elemental analysis, FT-IR, H NMR, CNMR and single crystal X-ray diffraction techniques. Both compounds 1 and 2 crystallized in orthorhombic crystal system with Pbca and P212121 space group respectively, having the unit cell parameters: a = 11.7220(12) Å, b = 14.4580(13) Å, c = 15.7853(12) Å, β = 90°, Volume = 2675.2(4) Å, Z = 8 for 1 and a = 6.1146(5) Å, b = 9.0567(8) Å, c = 26.079(3) Å, β = 90°, Volume = 1444.2(2) Å, Z = 4 for compound 2. The crystal structures of both compounds ( 1 and 2) are stabilized by N-H···O strong intermolecular hydrogen bonding forming C( 8) motifs. In compound 1, the molecules are linked by three C-H···O intramolecular H-bond forming S( 6) motifs. In compound 2, the molecules are linked by C-H···N intermolecular H-bond exhibiting C( 12) motif and C-H···O intramolecular H-bond leading to S( 5) motif. Crystallographic and vibrational data are compared with the results of density functional theory (DFT) method at the B3LYP/6-31G(d,p) level. The electronic (UV-vis) spectra was calculated by using the TD-DFT method and correlated with experimental spectra. Graphical Abstract: The crystal structure of compound 1, formed four motifs which are giving first-level graph set N: C( 8) S( 6) S( 6) S( 6) while compound 2, formed three motifs, giving first-level graph set N: C( 8) C( 12) S( 5) and second-level graph set N( a, b): C( 14). Crystallographic and vibrational (IR) data were compared with the results of density functional theory (DFT) method at the B3LYP/6-31G(d,p) level and electronic (UV-vis) spectra was calculated by using the TD-DFT method.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]