تحضير وتقييم الفعالية المضادة للبكتريا لمشتقات 4،3،1-اوكساديازول جديدة حاملة لوحدة الازتيدين-2-ون

Synthesis and Antibacterial Evaluation of New 1,3,4-Oxadiazole Derivatives Bearing Azetidin-2-one Moiety

Abstract
Heterocyclic compounds are among the most important structural classes in medicinal chemistry, particularly those containing nitrogen and sulfur atoms. β-Lactam rings, found in numerous antibiotics, have proven to be essential pharmacophores in antimicrobial therapy due to their ability to inhibit bacterial cell wall synthesis. In this work, a new series of 1,3,4-oxadiazole derivatives bearing azetidin-2-one moieties were synthesized via multi-step reactions as outlined in Schemes (I) and (II).
The aim of this research was to design and synthesize new hybrid molecules combining oxadiazole and β-lactam pharmacophores, evaluate their structural features.
The starting material 5-(4-Aminophenyl)-2-thiol-1,3,4-oxadiazole (A) has been prepared by refluxing 4-aminobenzoyl hydrazide and carbon disulfide in presence of potassium hydroxide in absolute ethanol. The amino function of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol (A) has been diazotized by hydrochloric acid and sodium nitrite and the generating oxadiazolyldiazonium chloride was directly coupled with sodium phenoxide salts of ortho-Vanillin (2-hydroxy-3-methoxybenzaldehyde) and with salicylaldehyde (2-hydroxy benzaldehyde) to produce azoic aldehydes of oxadiazole (B) and (E), respectively. The azoic aldehydes (B) and (E) were subsequently condensed with a number of aniline derivatives (2-methoxyaniline, 2,4-dimethylaniline, 4-aminophenol, 2-chloroaniline, 2,4-dichloroaniline, and 3-nitroaniline), through microwave technique to produced imine derivatives (C1-C5) and (F1-F6). Imines were subsequently reacted with chloroacetic chloride via cyclization reaction usage microwave method in dimethylformamide producing new azetidin-2-ones (β-lactams) of 1,3,4-oxadiazole (D1-D5) and (G1-G6).
Correspondingly, the structures of the desired azetidin-2-one compounds were proven from infrared (IR), proton nuclear magnetic resonance (1H NMR), and Mass spectroscopic techniques.
Azetidin-2-ones (β-lactams) represent as a strong class of heterocyclic chemicals in the pharmaceutical industry, compelling scientists to synthesize and test new medications. The actions athwart bacteria of the new azetidin-2-one compounds have been screened via using method of agar diffusion on Gram-negative and Gram-positive germs in dimethyl sulfoxide as solvent. The new synthesized azetidin-2-one compounds are containing relatively high ratio of nitrogen as well as sulfur that may be caused rise in biological activity. The new azetidine-2-one compounds (D4, D5, G1, G2 and G4) showed activities against Gram-negative bacteria Escherichia coli, greater than reference drug (amoxicillin-clavulanate), whereas compounds (D1, D2, and D3) expressed better action than the reference drug against Gram-positive bacteria Staphylococcus aurous.

SCHEME (I). Synthesis of β-lactam derivatives (D1- D5)

SCHEME (II). Synthesis of β-lactam derivatives (G1-G6)