SYNTHESIS and ANTIMICROBIAL ACTIVITY of NOVEL
DISUBSTITUTED OXADIAZOLE DERIVATIVES
Ulviye Acar Çevik1, Yusuf Özkay1, Juan Bueno2, Fatih Demirci3
1
AnadoluUniversity, Faculty of Pharmacy, Depatment of PharmaceuticalChemistry, Eskişehir-Turkey
2
Infection and Cancer Group, School of Medicine, University of Antioquia, Medellín, Colombia
Anadolu University, Faculty of Pharmacy, Department of Pharmacognosy, Eskişehir, Türkiye
3
Today, there are many drugs on market for microbial infections, but also lots of research still
keeps continuing in this area on account of the unsatisfactory status of present treatment of
microorganisms, drug side effects, toxic effects and the acquisition by the infecting organisms
of the resistance to the present drugs.
The 1,3,4-oxadiazole derivatives have been found to exhibit antimicrobial [1, 2].
Benzimidazole compounds have also important role on the treatment of bacterial infections.
Benzimidazole is structurally similar to purine, and its derivatives could compete with
purines. In the view of such information, we design a new series of 2-((5-(4-(1Hbenzo[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)thio)-derivatives.
The reaction of o-phenylenediamine and methyl 4-formylbenzoate in DMF under microwave
condition, gave methyl 4-(1H-benzo[d]imidazol-2-yl)benzoate (1). The compound 1 was
treated with hydrazine hydrate to afford 4-(1H-benzo[d]imidazol-2-yl)benzohydrazide (2).
The reaction of compound 2 with CS2 in the presence of NaOH gave 5-(4-(1Hbenzo[d]imidazol-2-yl)phenyl)-1,3,4-oxadiazole-2-thiol (3), which was reacted with
substituted bromide derivatives to obtain final compounds.
Structures of the compounds were confirmed by IR, 1H-NMR, 13C-NMR and MS
spectroscopic data and Elemental analyses results. Antimicrobial activities of the compounds
against resistant human pathogenic microorganisms were evaluated according to the CLSI
methods [3,4]. Final products were tested for their in vitro growth inhibitory activity against
human pathogenic Escherichia coli (ATCC 35218), Escherichia coli (ATCC 25922),
Staphylococcus aureus (ATCC 25923), Pseudomona aeuroginosa (ATCC 27853), and yeast
as Candida albicans (ATCC 90028), Candida glabrata (ATCC 90030), Candida krusei
(ATCC 6258), and Candida parapsilosis (ATCC 22019), Chloramphenicol and ketoconazole
were used as control drugs.
In the series, 4c was the most active derivative against all tested bacteria, where some of the
compounds also displayed good antibacterial and anticandidal activity within the different
inhibition extents.
References
[1] P. Karegoudar, M. S. Karthikeyan, D. J. Prasad, M. Mahalinga,B. S. Holla, and N. S. Kumari, “Synthesis of some novel
2,4-disubstituted thiazoles as possible antimicrobial agents,” European Journal ofMedicinal Chemistry, vol. 43, no. 2, pp.
261–267, 2008.
[2] O. Prakash, M. Kumar, R. Kumar, C. Sharma, and K. R. Aneja, “Hypervalent iodine(III) mediated synthesis of novel
unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles as antibacterial and antifungal agents,” European Journal of Medicinal
Chemistry, vol. 45, no. 9, pp. 4252–4257, 2010.
[3] Clinical and Laboratory Standarts Institue (CLSI). (Formerly NCCLS) Methods for dilution antimicrobial sceptibilitytests
for bacteria that grow aerobically, CLSI M7-A7, Clinical and Laboratory Standards Institue, 940 West Valley Road,Wayne,
Pennsylvania, USA (2006).
[4] Clinical and Laboratory Standards Institute (CLSI) 2008, Reference Method for Broth Dilution Antifungal
SusceptibilityTesting of Yeast, Approved Standard, CLSI 27-A3, 3rd ed., PA, USA.