Synthesis of new pyrazoles, thiadiazoles, and trizolotriazines compounds that act as an antibacterial agents using C-ethoxycarbonylhydrazonoyl chloride precursor: Molecular docking simulation and in silico ADMET prediction studies

Author: Saleh, Fatma M. ; Hassaneen, Hamdi M. ; Laboud, Yara N. ; Zahran, Doaa

Treatment of C-ethoxycarbonylhydrazonoyl chloride with active methylene-containing compounds such as dibenzoylmethane or malononitrile in sodium ethoxide solution yielded in each case pyrazole derivativesThe latter pyrazoles were used as a useful precursors in the synthesis of new heterocyclic compounds like pyrazoles and 1,3,4-thiadizaoles upon reaction with hydrazonoyl halides.Also, the reaction of C-ethoxycarbonylhydrazonoyl chloride with the appropriate triazinethiones in chloroform in the presence of catalytic amount of triethylamine at reflux yielded the corresponding triazolotriazines.The structures of the newly synthesized compounds were confirmed based on elemental analyses and spectral data.The antibacterial activities were studied against two gram-pos. and two gram-neg. bacteria, the results represented that compound Et 1-(4-acetylphenyl)-6-benzyl-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate showed antibacterial activity against Salmonella (22 mm) and E. coli (6 mm), as well as compound Et 1-(4-acetylphenyl)-6-(4-methylbenzyl)-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate against Salmonella (5 mm) and Staphylococcus aureus (10 mm) while the rest compounds showed no antibacterial activities.The mol. docking simulation was investigated for the most active compounds Et 1-(4-acetylphenyl)-6-benzyl-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate and Et 1-(4-acetylphenyl)-6-(4-methylbenzyl)-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate.The results confirm that compounds Et 1-(4-acetylphenyl)-6-benzyl-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate and Et 1-(4-acetylphenyl)-6-(4-methylbenzyl)-5-oxo-1,5-dihydro-[1,2,4]triazolo[4,3-b][1,2,4]triazine-3-carboxylate are promising candidates for potential inhibitors of DNA gryA (P37411) of Salmonella and Transpeptidases (Q2FV99) of Staphylococcus aureus.

01 Nov 2024·Russian Journal of General Chemistry

Synthesis and Biological Properties of Hybrid Compounds Based on Nitrogen-Containing Heterocycles and 1,5-Disubstituted 3,7-Diazabicyclo[3.3.1]nonan-9-ones

Author: Sargsyan, A. S. ; Safaryan, M. S. ; Madoyan, R. A. ; Hambardzumyan, A. A. ; Harutyunyan, A. A. ; Hakobyan, M. R. ; Karapetyan, H. A. ; Danghyan, M. Yu. ; Harutyunyan, A. D. ; Mnatsakanyan, A. A. ; Israelyan, S. G. ; Gevorkyan, K. A. ; Gasparyan, S. P. ; Sukiasyan, A. G. ; Panosyan, H. A.

The reaction of aromatic aldehydes and 3-(heteryl)methyl-4-methoxybenzaldehydes with 1,5-disubstituted 3,7-diazabicyclo[3.3.1]nonan-9-ones afforded 2-aryl(hetaryl)-5,7-dimethyl-1,3-diazaadamantane-6-ones.3-(Heteryl)methyl-4-methoxybenzaldehydes were obtained by alkylation of nitrogen-containing heterocycles (N1-functionalized uracil and 5-halouracils, N3-functionalized 6-methylpyrimidin- and quinazolin-4(3H)-ones, benzotriazole, quinoline, benzoxazole) with 3-chloromethyl-4-methoxylbenzaldehyde.Antibacterial and fungicidal properties of the synthesized compounds were studied.

01 Nov 2024·Russian Chemical Bulletin

Theoretical study of stability of dinitrosyl iron(i) complexes with thiocarbonyl ligands

Author: Sanina, N. A. ; Luzhkov, V. B. ; Krapivin, V. B.

The binding energies of thioligands L of the general formula S=CR₁R₂ in dinitrosyl iron complexes [Fe(NO)₂L₂]⁺ (DNICs) were calculated using d. functional theory methods.The TPSSH functional with the def2-TZVP basis set and the PCM-SMD polarizable continuum model were used.The reactions of abstraction of 14 thioamide and thiocarbonyl ligands and their replacement with a H₂O mol. in the gas phase and aqueous medium were studied.It is found that the bond energies in the gas phase do not accurately characterize the stability of DNICs because of the high energy of reorganization of the reaction products upon their transition into the aqueous phase.Anal. of the structure-activity correlations revealed linear regression dependences of Fe-S bond energies on partial charges on S atoms and electronegativity of thioligands.

100 Deals associated with Methylthiouracil

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KEGG	Wiki	ATC	Drug Bank
D07231	Methylthiouracil	H03BA01	DB13644

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