Document Type : Final File


1 Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Islamic Republic of Iran

2 Young Researchers and Elite Club, Neyshabur Branch, Islamic Azad University, Neyshabur, Islamic Republic of Iran


In recent years, the spread of drug-resistant strains of Streptococcus pneumoniae, as the most common causes of bacterial respiratory infections, threatens public health. Therefore, the use of new antimicrobial medicines to inhibit this pathogen is an urgent demand. In this research project, the inhibitory effects of thirty recently synthesized compounds including thiazole, thiazolidine, imidazole, tetrahydropyrimidine, oxazolidine and thiazepine derivatives against this bacterium have been studied as well. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), zone diameters of bacterial growth inhibition were also measured by a disk diffusion method. All the obtained results were compared with antibacterial effects of gentamicin and penicillin antibiotics. Among all investigated compounds, only derivatives 3d, 5a, 5b, 7, 9c, 15, 17c and 17d showed inhibitory effects against S. pneumonia. As a result, the most and least effects respectively belonged to thiazole derivative 15 and thiazepine derivative 17c with zone diameters of bacterial growth inhibition= 20.2, 9.3 mm, MIC= 64, 2048 μg/mL and MBC= 128, 4096 μg/mL. Whereas thiazole derivative 15 exhibited a good inhibitory activity against the mentioned pathogen, it can be replaced as a good agent instead of antibiotics.


  1. Zielnik-Jurkiewicz B. and Bielicka A. Antibiotic resistance of Streptococcus pneumoniae in children with acute otitis media treatment failure. Int. J. Pediatr. Otorhinolaryngol. 79 (12): 2129-2133 (2015).
  2. Nakano S., Fujisawa T., Ito Y., Chang B., Suga S. and Noguchi T. Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012-2014. Vaccine 34 (1): 67-76 (2016).
  3. Yang X. Y., Zhang L., Liu J., Li N., Yu G. and Cao K. Proteomic analysis on the antibacterial activity of a Ru(II) complex against Streptococcus pneumoniae. J. Proteomics 115: 107-116 (2015).
  4. Shariatifar N., Rezae M., Sayadi M., Mosha M. H., Saeedi M. and Mohammadhosseini N. In-vitro antibacterial evaluation of some fluoroquinolone derivatives against food borne bacteria. J. Sci. I. R. Iran 27 (2): 129-133 (2016).
  5. Khalil A. M., Berghot M. A. and Gouda M. A. Synthesis and antibacterial activity of some new thiazole and thiophene derivatives. Eur. J. Med. Chem. 44 (11): 4434-440 (2009).
  6. Desai N., Dodiya A. and Shihory N. Synthesis and antimicrobial activity of novel quinazolinone–thiazolidine–quinoline compounds. J. Saudi Chem. Soc. 17 (3): 259-267 (2013).
  7. Cheng Y., Yin M., Ren X., Feng Q., Wang J. and Zhou Y. A coordination polymeric gelator basedon Ag (I) and 2, 7-bis (1-imidazole) fluorene: Synthesis, characterization, gelation and antibacterial properties. Mater. Lett. 139: 141-144 (2015).
  8. Aridoss G., Amirthaganesan S. and Jeong Y. T. Synthesis, crystal and antibacterial studies of diversely functionalized tetrahydropyridin-4-ol. Bioorg. Med. Chem. Lett. 20 (7): 2242-2249 (2010).
  9. Ammazzalorso A., Amoroso R., Bettoni G., Fantacuzzi M., De-Filippis B. and Giampietro L. Synthesis and antibacterial evaluation of oxazolidin-2-ones structurally related to linezolid. Farmaco 59 (9): 685-690 (2004).
  10. 10.  Malik G. M., Tailor J. H., Zadafiya S. K. and Rajani D. Synthesis and biological activity of triazolo derivative of Dibenzothiazepine. Chem. Biol. Interface 5 (3): 208-218 (2015).
  11. 11.  Cheng K., Xue J. Y. and Zhu H. L. Design, synthesis and antibacterial activity studies of thiazole derivatives as potent ecKAS III inhibitors. Bioorg. Med. Chem. Lett. 23 (14): 4235-4238 (2013).
  12. 12.  Moreira T. L., Barbosa A. F., Veiga-Santos P., Henriques C., Henriques-Pons A. and Galdino S.L. Effect of thiazolidine LPSF SF29 on the growth and morphology of Trypanosoma cruzi. Int. J. Antimicrob. Agents 41 (2): 183-187 (2013).
  13. 13.  Desai N. C. and Dodiya A. M. Synthesis, characterization and antimicrobial screening of quinoline based quinazolinone-4-thiazolidinone heterocycles. Arab. J. Chem. 7 (6): 906-913 (2014).
  14. 14.  Ghasemi B., Beyzaei H. and 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. 22 (1): 54-59 (2016).
  15. 15.  Ghasemi B., Beyzaei H. and Hashemi H. Study of antibacterial effect of novel thiazole, imidazole, and tetrahydropyrimidine derivatives against Listeria monocytogenes. Ann. Mil. Health Sci. Res. 13 (3): 101-105 (2015).
  16. 16.  Park S. J., Kang S. H., Kang Y. K., Eom Y. B., Koh K. O. and Kim D. Y. Inhibition of homodimerization of toll-like receptor 4 by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester. Int. Immunopharmacol. 11 (1): 19-22 (2011).
  17. 17.  Deng B. L., Zhao Y., Hartman T. L., Watson K., Buckheit R.W. and Pannecouque C. Synthesis of alkenyldiarylmethanes (ADAMs) containing benzo[d]isoxazole and oxazolidin-2-one rings, a new series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Eur. J. Med. Chem. 44 (3): 1210-1214 (2009).
  18. 18.  Ansari F. L., Iftikhar F., Ul-Haq I., Mirza B., Baseer M. and Rashid U. Solid-phase synthesis and biological evaluation of a parallel library of 2,3-dihydro-1,5-benzothiazepines. Bioorg. Med. Chem. 16 (16): 7691-7697 (2008).
  19. 19.  Beyzaei H., Aryan R. and Gomroki M. Synthesis of novel heterocyclic 2-(2-ylidene)malononitrile derivatives. Org. Chem. Indian J. 11 (1): 3-10 (2015).
  20. 20.  Beyzaei H., Aryan R. and Keshtegar Z. Synthesis of new imidazolidine and tetrahydropyrimidine derivatives. Adv. Chem. ID: 834641 (2014).
  21. 21.  Bakavoli M., Beyzaei H., Rahimizadeh M. and Eshghi H. Regioselective synthesis of new 2‐(E)‐cyano(oxazolidin‐2‐ylidene)thiazoles. Eur. J. Chem. 2 (3): 356‐358 (2011).
  22. 22.  Bakavoli M., Beyzaei H., Rahimizadeh M., Eshghi H. and Takjoo R. Regioselective synthesis of new 2-(E)-cyano(thiazolidin-2-ylidene)thiazoles. Molecules 14: 4849‐4857 (2009).
  23. 23.  Bakavoli M., Beyzaei H., Rahimizadeh M. and Eshghi H. Regioselective synthesis of 2[(E)-(benzo[d]thiazol-2(3H)ylidene)(cyano)methyl]thiazoles. Heterocycl. Commun. 17 (3-4): 151-154 (2011).
  24. 24.  Bakavoli M., Beyzaei H., Rahimizadeh M. and Eshghi H. One-pot synthesis of functionalized tetrahydro-1,4-thiazepines. Synth. Commun. 41 (8): 1181-1185 (2011).
  25. 25.  Juspin T., Laget M., Terme T., Azas N. and Vanelle P. TDAE-assisted synthesis of new imidazo[2,1-b]thiazole derivatives as anti-infectious agents. Eur. J. Med. Chem. 45 (2): 840-845 (2010).
  26. 26.  Ghasemi B., Sanjarani G., Sanjarani Z. and Majidiani H. Evaluation of anti-bacterial effects of some novel thiazole and imidazole derivatives against some pathogenic bacteria. Iran. J. Microbiol. 7 (5): 281-286 (2015).
  27. 27.  Brvar M., Perdih A., Oblak M., Masic L.P. and Solmajer T. In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel inhibitors of DNA gyrase B. Bioorg. Med. Chem. Lett. 20 (3): 958-962 (2010).
  28. 28.  Lu X., Liu X., Wan B., Franzblau S. G., Chen L. and Zhou C. Synthesis and evaluation of anti-tubercular and antibacterial activities of new 4-(2,6-dichlorobenzyloxy)phenyl thiazole, oxazole and imidazole derivatives. Eur. J. Med. Chem. 49: 164-171 (2012).
  29. 29.  Bartels H. and Bartels R. Simple, rapid and sensitive determination of protionamide in human serum by high-performance liquid chromatography. J. Chrom. B Biomed. Sci. Appl. 707 (1-2): 338-341 (1998).
  30. 30.  Xue T., Ding S., Guo B., Chu W., Wang H. and Yang Y. Synthesis and structure–activity relationship studies of novel [6, 6, 5] tricyclic oxazolidinone derivatives as potential antibacterial agents. Bioorg. Med. Chem. Lett. 25 (10): 2203-2210 (2015).
  31. 31.  Rajkumar R., Kamaraj A. and Krishnasamy K. Synthesis, spectral characterization and biological evaluation of novel 1-(2-(4, 5-dimethyl-2-phenyl-1H-imidazol-1-yl) ethyl) piperazine derivatives. J. Saudi Chem. Soc. 18 (5): 735-743 (2014).



 Wang S.F., Yin Y., Wu X., Qiao F., Sha S. and Lv P.C. Synthesis, molecular docking and biological evaluation of coumarin derivatives containing piperazine skeleton as potential antibacterial agents. Bioorg. Med. Chem. 22 (21): 5727-5737 (2014).

  1. 33.  Madabhushi S., Mallu K. K., Vangipuram V. S., Kurva S., Poornachandra Y. and Ganesh Kumar C. Synthesis of novel benzimidazole functionalized chiral thioureas and evaluation of their antibacterial and anticancer activities. Bioorg. Med. Chem. Lett. 24 (20): 4822-4825 (2014).
  2. 34.  Elumalai K., Ashraf Ali M., Elumalai M., Eluri K. and Srinivasan S. Novel isoniazid cyclocondensed 1,2,3,4-tetrahydropyrimidine derivatives for treating infectious disease: a synthesis and in vitro biological evaluation. J. Acute Dis. 2 (4): 316-321 (2013).
  3. 35.  Akhaja T. N. and Raval J. P. Design, synthesis, in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antibacterial, antifungal and anti-tubercular agents. Chin. Chem. Lett. 23 (4): 446-449 (2012).
  4. 36.  Kumar M., Sharma K., Kumar Fogla A., Sharma K. and Rathore M. Synthesis and antimicrobial activity of 2,4-diaryl-2,3-dihydrobenzo[b][1,4]thiazepines. Res. Chem. Intermediat. 39 (6): 2555-2564 (2013).