Synthesis and Antibacterial Activity of New Hybrid Molecules Containing 1,3,4-Thiadiazole and 1,3,4-Oxadiazole Bearing Ibuprofen Moiety

Rusul K. Fadhel  Fadhel; Jumbad H.  Tomma

doi:10.30526/39.3.4453

Authors

Rusul K. Fadhel Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0007-6483-9736
Jumbad H. Tomma Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0003-4625-8341

DOI:

https://doi.org/10.30526/39.3.4453

Keywords:

Antibacterial, Heterocyclic, Ibuprofen, 1,3,4-Oxadiazole, 1,3,4- Thiadiazole

Abstract

A series of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole moieties bearing an ibuprofen moiety were designed, synthesized, and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. A carboxylic acid compound with a 1,3,4-thiadiazole unit was synthesized via the coupling reaction of 5-(1-(4-isobutylphenyl) ethyl)-1,3,4-thiadiazol-2-amine with benzoic acid. This compound was then used as the starting material to make several new 1,3,4-oxadiazole derivatives through ring closure reactions, after first converting it to its ester (methyl 4-(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-yl) benzoate) and then to the acid hydrazide (4-(5-(1-(4-isobutylphenyl) ethyl)-1,3,4-thiadiazol-2-yl)benzohydrazide). Finally, the intramolecular ring closure of the hydrazide compound with carboxylic acids under reflux in POCl₃ afforded 2-(4-(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-yl)phenyl)1,3,4-oxadiazole derivatives. The synthesized compounds were characterized using spectroscopic techniques, including IR, ¹H NMR, and ¹³C NMR. The compounds were tested for antibacterial activity on two Gram-positive (Streptococcus pyogenes and Staphylococcus aureus) and two Gram-negative (Escherichia coli and Proteus mirabilis) bacterial strains. The prepared compounds demonstrated significant antibacterial activity compared with Ibuprofen and Ampicillin. The maximum inhibition zones were recorded against Staphylococcus aureus (20 mm), Proteus (18 mm), Escherichia coli (17 mm), and Streptococcus (17 mm), suggesting that the synthesized derivatives possess promising antibacterial properties. This difference resulted from substituting the benzene ring with various substituents.

Author Biographies

Rusul K. Fadhel , Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq

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Jumbad H. Tomma , Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq

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