Hamid Beyzaei Abbas Jamshidian Mohammad Reza Hajinezhad Seyed Hadi Hashemi Nasim Amel Maliheh Abdollahi Fatemeh Arab-Sahebi Behzad Ghasemi


The spread of antibiotic-resistant bacteria in many humans and animals has driven researches to identify and design novel antibacterial agents. In vitro inhibitory activity of (2E)-2-(4,5-dihydro-4-oxothiazol-2-yl)-2-(thiazolidin-2-ylidene) acetonitrile against many bacterial pathogens has been proven in both veterinary and human medicine. In this study, its in vivo toxic effects was studied in mice. The median lethal dose (LD50) value of 239.88 mg/kg was estimated using intraperitoneal injection in 8 groups of mice after 48 h treatment. Then, intraperitoneal injections of LD50 of oxothiazole solution into 4 other mice were done to evaluate histopathological changes in their liver and kidney tissues. The histopathological studies were identified as fatty change, hepatitis, necrosis and regeneration in liver, and fibrosis, necrosis, nephritis, hyaline cast and hyperaemia in kidney. In conclusion, the synthesized oxothiazole derivative causes renal and hepatic toxicity in mice at medium concentrations. The change of thiazole substituents and complexation may reduce its toxicity.

Article Details


Toxic effects, Histopathological study, Oxothiazole derivative

1. Wang D, Zhang L, Zhou X, He Y, Yong C, Shen M, et al. Antimicrobial
susceptibility, virulence genes, and randomly amplified
polymorphic DNA analysis of Staphylococcus aureus
recovered from bovine mastitis in Ningxia, China.J Dairy Sci.
2. Ahumada-Santos YP, Soto-Sotomayor ME, Baez-Flores ME,
Diaz-Camacho SP, Lopez-Angulo G , Eslava-Campos CA, et
al. Antibacterial synergism of Echeveria subrigida (B. L. Rob
& Seaton) and commercial antibiotics against multidrug resistant
Escherichia coli and Staphylococcus aureus.Eur J Int
Med. 2016;8(5):638-44.
3. Santos L, Ramos F. Analytical strategies for the detection and
quantification of antibiotic residues in aquaculture fishes: A
review. Trends Food Sci Technol. 2016;52:16-30.
4. Bakavoli M, Beyzaei H, Rahimizadeh M, Eshghi H. Regioselective
synthesis of 2[(E)(benzo[d]thiazol2(3H)ylidene)(cyano)
methyl]thiazoles. Heterocycl Commun. 2011;17:151-4.
5. Ghasemi B, Sanjarani G, Sanjarani Z, Majidiani H. Evaluation
of anti-bacterial effects of some novel thiazole and imidazole
derivatives against some pathogenic bacteria. Iran J Microb.
6. Beyzaei H, Aryan R, Molashahi H, Zahedi MM, Samzadeh-
Kermani A Ghasemi B. MgO nanoparticle-catalyzed, solvent-
free Hantzsch synthesis and antibacterial evaluation of
new substituted thiazoles. J Iran Chem Soc. 2017;14(5):1023-
7. Pawar CD, Sarkate AP, Karnik KS, Bahekar SS, Pansare DN,
Shelke RN, et al. Synthesis and antimicrobial evaluation of
novel ethyl 2-(2-(4-substituted)acetamido)-4-subtituted-thiazole-
5-carboxylate derivatives. Bioorg Med Chem Lett.
8. Qin YJ, Wang PF, Makawana JA, Wang ZC, Wang ZN,Gu Y,et
al. Design, synthesis and biological evaluation of metronidazole–
thiazole derivatives as antibacterial inhibitors. Bioorg
Med Chem Lett. 2014;24(22):5279-83.
9. Washburn DG, Holt DA, Dodson J, McAtee JJ, Terrell LR,
Barton L, et al. The discovery of potent blockers of the canonical
transient receptor channels, TRPC3 and TRPC6, based
on an anilino-thiazole pharmacophore. Bioorg Med Chem
Lett. 2013;23:4979-84.
10. Kang SY, Song KS, Lee J, Lee SH, Lee J. Synthesis of pyridazine
and thiazole analogs as SGLT2 inhibitors. Bioorg Med
Chem Lett. 2010;18:6069-79.
11. Andreani A, Granaiola M, Guardigli M, Leoni A, Locatelli
A, Morigi R, et al. Synthesis and chemiluminescent high
throughput screening for inhibitionof acetylcholinesterase
activity by imidazo[2,1-b]thiazole derivatives. Eur J Med
Chem. 2005;40:1331-4.
12. Andreani A, Granaiola M, Leoni A, Locatelli A, Morigi R,
Rambaldi M. Effects of new ubiquinone-imidazo[2,1-b]thiazoles
on mitochondrial complex I (NADH-ubiquinone reductase)
and on mitochondrial permeability transition pore.
Bioorg Med Chem Lett. 2004;12:5525-32.
13. Ghasemi B, Beyzaei H, Hashemi SH,
Majidiani H. Study of antibacterial
effect ofnovel thiazole, imidazole and
tetrahydropyridine derivatives against
Escherichia coli. J Med Bacteriol.
14. Ghasemi B, Beyzaei H, Hashemi SH.
Study of antibacterial effect of novel
thiazole, imidazole, and tetrahydropyrimidine
derivatives against Listeria
Monocytogens. Ann Mil Health Sci
Res. 2015;13:101-5.
15. Ghasemi B, Najimi M, Beyzaei H,
Jamshidian A. Antibacterial effects
of novel thiazole derivatives and
the toxicity of oxothiazole on liver
histopathology of mice. Med Lab J.
16. Ghasemi B , Beyzaie H , Majidiani
H.A comparative study on the antibacterial
effects of some newly synthesized
thiazole, imidazolidine and tetrahydropyrimidine
derivatives against
Bacillus cereus and Salmonella typhimurium.
Pharm Sci. 2016;22(1):54-9.
17. Chen H, Song J, Wang J, Xu C, Chen
C, Gu W. Synthesis and biological
evaluation of thiazole derivatives as
novel USP7 inhibitors. Bioorg Med
Chem Lett. 2017;27(4):845-9.
18. Reichelt A, Bailis JM, Bartberger MD,
Yao G, Shu H, Kaller MR. Synthesis
and structure-activity relationship
of trisubstituted thiazoles as Cdc7
kinase inhibitors. Eur J Med Chem.
19. Chen YL, Cherry K, Michael L, Ebbinghaus
CF, Gamlath CB, Liston D.
Thiazole-diamides as potent γ-secretase
inhibitors. Bioorg Med Chem
Lett. 2007;17(20):5518-22.
20. Prinsen MK, Romijn T, Snoeij NJ. Skin
sensitization testing: the relevance of
rechallenge and pretreatment with sodium
lauryl sulfate in the guinea pig
maximization test. Food Chem Toxicol.
21. Love BL, Barrons R, Veverka A, Snider
KM. Urate-lowering therapy for gout:
focus on febuxostat. Pharmacother.
22. Keating, GM. Dasatinib: A review
in chronic myeloid leukaemia and
Ph+ acute lymphoblastic leukaemia.
Drugs. 2017;77(1):85-9.
23. Abd El-Galil EA, Sabrry NM, Abdalla
MM, Abdel-Wahab BF. Synthesis, antiarrhythmic
and anticoagulant activities
of novel thiazolo derivatives from
methyl 2-(thiazol-2-ylcarbamoyl)acetate.
Eur J Med Chem. 2009;44:725-35.
24. Siddiqui N, Ahsan W. Triazole incorporated
thiazoles as a new class
of anticonvulsants: Design, synthesis
and in vivo screening. Eur J Med
25. Andreani A, Rambaldi M, Mascellani
G, Rugarli P. Synthesis and diuretic
activity of imidazo[2,1-b]thiazole
acetohydrazones. Eur J Med Chem.
26. Wang G, Deng C, Xie C, Ma L, Yang
J, QiuN, et al. Synthesis and biological
evaluation of novel dimethyl[1,10-biphenyl]-
2,20-dicarboxylate derivatives
containing thiazolidine-2,4-dione for
the treatment of concanavalin A-induced
acute liver injury of BALB/c
mice. Eur J Med Chem. 2011;46:5941-
27. Yang H, Zhang W, Kong Q, Liu H, Sun
R, Lin B, et al. Effects of pubertal exposure
to thiazole-Zn on thyroid function
and development in female rats.
Food Chem Toxicol.2013;53:100-4.
28. Bakavoli M, Beyzaei H, Rahimizadeh
M, Eshghi H, Takjoo R. Regioselective
synthesis of new 2-(E)-cyano(thiazolidin-
2-ylidene)thiazoles. Molecules.
How to Cite
Hamid, B., Abbas, J., Mohammad Reza, H., Seyed Hadi, H., Nasim, A., Maliheh, A., Fatemeh, A.-S., & Behzad, G. (2019). Study of Toxic Effects of Oxothiazole Derivative as a New Antibacterial Agent. Iranian Journal of Veterinary Science and Technology, 10(2), 17-21. https://doi.org/10.22067/veterinary.v2i10.71626
Original Articles