732242-02-3Relevant articles and documents
Synthesis, hypoglycemic effect, antimicrobial and molecular docking studies of organotin(IV) complexes derived from N -phthalimido β-amino acid derivatives
Ahmed, Muhammad M.,Riaz, Nagina N.,Kashif, Muhammad,Ashfaq, Muhammad,Arshad, Muhammad N.,Sajid, Muhammad
, p. 1082 - 1099 (2021/05/19)
N-Phthalimido β-amino acid derivatives, 3-phthalimido-3(2-hydroxyphenyl) propanoic acid (P2HPA) and 3-phthalimido-3(2-nitrophenyl) propanoic acid (P2NPA) with new series of diand triorganotin(IV) complexes (1-12) have been designed and synthesized. All the ligands and organotin(IV) complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H, 13C, 119Sn) spectroscopy and electron ionization mass spectrometry (EI-MS). Synthesized ligands and complexes were screened to determine the antibacterial activity and results showed that the triorganotin(IV) complexes have better activity compared to diorganotin(IV) complexes and ligands. In addition, molecular docking analysis of ligands on the catalytic pocket of sortase A (PDB ID 1T2W) showed that the ligands can bind the active amino acid residues in the pocket. The antioxidant activity was also performed by the DPPH (1,1-diphenyl-2-picrylhydrazyl radical) method and complexes showed better results than ligands. The compounds were also tested in vivo to determine the hypoglycemic activities on different groups of alloxan induced diabetic rabbits. The complexes (1-6) were found better hypoglycemic agents as they stabilized the glucose level to about 175-105 mg dL-1 as compared to ligand P2HPA.
Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase
Kashif, Muhammad,Chacón-Vargas, Karla Fabiola,López-Cedillo, Julio Cesar,Nogueda-Torres, Benjamín,Paz-González, Alma D.,Ramírez-Moreno, Esther,Agusti, Rosalia,Uhrig, Maria Laura,Reyes-Arellano, Alicia,Peralta-Cruz, Javier,Ashfaq, Muhammad,Rivera, Gildardo
, p. 252 - 268 (2018/07/14)
In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (?11.1 kcal/mol) compared to reference DANA (?7.8 kcal/mol), a natural ligand for TS enzyme. Furthermore, the 3D and 2D interactions analysis of compound D-11 showed a hydrogen bond, π-π stacking, π-anion, hydrophobic and Van der Waals forces with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59) on the active site of TcTS. Additionally, D-11 showed the highest TcTS enzyme inhibition (86.9% ± 5) by high-performance ion exchange chromatography (HPAEC). Finally, D-11 showed better trypanocidal activity than the reference drugs nifurtimox and benznidazole with an equal % lysis (63 ± 4 and 65 ± 2 at 10 μg/mL) and LC50 value (52.70 ± 2.70 μM and 46.19 ± 2.36 μM) on NINOA and INC-5 strains, respectively. Therefore, D-11 is a small-molecule with potent TcTS inhibition and a strong trypanocidal effect that could help in the development of new anti-Chagas agents.
Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans
Varga, Andrea,Bánóczi, Gergely,Nagy, Botond,Bencze, László Csaba,To?a, Monica Ioana,Gellért, ákos,Irimie, Florin Dan,Rétey, János,Poppe, László,Paizs, Csaba
, p. 56412 - 56420 (2016/07/06)
In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.
