Structural analysis and molecular docking of potential ligands with chorismate synthase of Listeria monocytogenes: A novel antibacterial drug target.

Listeriosis, in particular that caused by Listeria monocytogenes, is a major foodborne pathogen, and its control is becoming difficult because of widespread emergence of drug resistance strains. Chorismate synthase (CS), an essential enzyme of shikimate pathway present only in bacteria, fungi, plant and some apicomplexan parasites, is a validated potential antimicrobial drug target. Antimicrobial development through the elucidation of essential structural features of the CS of L. monocytogenes (LmCS), identification and prioritization of potential lead compounds targeted against LmCS were done. Structure-based virtual screening and docking studies were performed using Autodock tools to retrieve potential candidates with high affinity binding against LmCS model from several ligand repositories. The potency of binding was also checked with other structurally similar CS from Streptococcus pneumoniae (SpCS) and Mycobacterium tuberculosis (MtCS). The sequence and structural studies revealed LmCS was similar to be other CS structures (1Q1L, 1QXO, 1R52, 1R53, 1SQ1, 1UM0, 1UMF, 1ZTB, 2011, 2012, 4ECD and 2G85) with each monomer presenting β-α-β sandwich topology with a central helical core. Molecular docking studies and ADME/Tox results revealed that ZINC03803450 and ZINC20149031 were most potent molecules binding into the active site of LmCS. Other two ligands ZINC13387711 and ZINC16052528 showed a strong binding affinity score against all three structures (LmCS, SpCS and MtCS) and bind to LmCS with the predicted inhibition constant (Ki) values of 22.94 nM and 35.84 nM, respectively. A reported benzofuran-3[2H]-one analog CHEMBL135212 with good ADME/Tox properties and experimental IC50 (nM) value of 7000 nM with SpCS could also be considered as a potential inhibitor of LmCS, as compared to previously reported 41 benzofuran-3[2H]-one analogs against SpCS. This information will assist in discovering those compounds that may act as potent CS inhibitors. Further experimental studies and evaluation of structure-activity relationship could help in the development of potential inhibitors against listeriosis, as well as antibacterial chemotherapy.

Synthesis and spectral studies of some transition metal complex of thymine and its 6- [arylazo] compound

Cobalt[II], nickel[II] and copper[II] acetates react with thymine compound [H[2]L] to form complexes having the general formula [M[H[2]L] [Ac][2]H[2]O, nH[2]O. However, the interaction of iron[III] chloride with thymine in acetic acid-water medium yields a new complex of the type [Fe[H[2]L][AC][3]H[2]O;J H[2]O. All the thymine complexes have been characterized by elemental analysis, infrared and electronic spectra where thymine acts as a neutral ligand and the acetate ion. behaves as a strong nucleophile during complexation. 6-[arylazo]thymine compound and its cobalt and copper complexes were synthesized and characterized where the ligand acts as a bidentate monobasic. All the complexes are with 1:1 stoichiometry. The azo group is not involved in the structure. 1[H]NMR spectrum of the azo compound was explained to give more information on the structure e of the investigated materials