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Synthesis and in vitro anti-Helicobacter pylori activity of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles

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Abstract

A new series of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles (6a–h) were synthesized and evaluated by the disc diffusion method against Helicobacter pylori. Four compounds which exhibited strong anti-H. pylori activity at concentration of 8–32 μg/disc (average of inhibition zone >20 mm) were further tested against 20 clinical isolates of H. pylori at lower concentrations. The averages of inhibition zone diameters indicated that all selected compounds exhibit better anti-H. pylori activity profile against clinical isolates of H. pylori with respect to standard drug metronidazole. Compound 6c, containing the 3-chlorobenzylthio moiety, was the most potent compound tested.

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References

  • Alemagna A, Bacchetti T, Beltrame P (1968) 1,3,4-Thiadiazoles-III:nucleophilic reactivity of 2-aryl-5-chloro-derivatives. Tetrahedron 24:3209–3217

    Article  CAS  Google Scholar 

  • Coudron PE, Stratton CW (1998) In-vitro evaluation of nitrofurantoin as an alternative agent for metronidazole in combination antimicrobial therapy against Helicobacter pylori. J Antimicrob Chemother 42:657–660

    Article  PubMed  CAS  Google Scholar 

  • Foroumadi A, Daneshtalab M, Shafiee A (1999) Synthesis and in vitro antifungal activity of 2-aryl-5-phenylsulfonyl-1,3,4-thiadiazole derivatives. Arzneim-Forsch Drug Res 49:1035–1038

    CAS  Google Scholar 

  • Foroumadi A, Asadipour A, Mirzaei M, Karimi J, Emami S (2002) Antituberculosis agents. V. Synthesis, evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(5-nitro-2-furyl)-1,3,4-thiadiazole derivatives. Farmaco 57:765–769

    Article  PubMed  CAS  Google Scholar 

  • Foroumadi A, Mansouri S, Kiani Z, Rahmani A (2003) Synthesis and in vitro antibacterial evaluation of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolones. Eur J Med Chem 38:851–854

    Article  PubMed  CAS  Google Scholar 

  • Foroumadi A, Pournourmohammadi S, Soltani F, Rezaee MA, Dabiri S, Kharazmi A, Shafiee A (2005) Synthesis and in vitro leishmanicidal activity of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1,3,4-thiadiazoles. Bioorg Med Chem Lett 15:1983–1985

    Article  PubMed  CAS  Google Scholar 

  • Foroumadi A, Siavoshi F, Safari F, Sheikholeslami A, Massarrat S (2006) Evaluation of in vitro antimicrobial effectiveness of novel nitroimidazole and nitrofuran derivatives against Helicobacter pylori. Helicobacter 11:398

    Google Scholar 

  • Graham DY (1998) Antibiotic resistance in H. pylori implications for therapy. Gastroenterology 115:1272–1277

    Article  PubMed  CAS  Google Scholar 

  • Iwakawa T, Nakai H, Sugimori G, Murabayashi A (2000) Reaction of 3-acetonyl-5-cyano-1,2,4-thiadiazole with phenylhydrazine hydrochlorides: indolization and phenylpyrazolation. Chem Pharm Bull 48:160–162

    PubMed  CAS  Google Scholar 

  • Jenks PJ, Ewards DI (2002) Metronidazole resistance in Helicobacter pylori. Int J Antimicrob Agents 19:1–7

    Article  PubMed  CAS  Google Scholar 

  • Jenks PJ, Labigne A, Ferrero RL (1999) Exposure to metronidazole in vivo readily induces resistance in Helicobacter pylori and reduces the efficacy of eradication therapy in mice. Antimicrob Agents Chemother 43:777–781

    Article  PubMed  CAS  Google Scholar 

  • Jenks PJ, Ferrero RL, Tankovic J, Thiberge JM, Labigne A (2000) Evaluation of nitrofurantoin combination therapy of metronidazole-sensitive and -resistant Helicobacter pylori infections in mice. Antimicrob Agents Chemother 44:2623–2629

    Article  PubMed  CAS  Google Scholar 

  • Kountouras J, Zavos C, Chatzopoulos D (2005) New concepts of molecular biology on gastric carcinogenesis. Hepatogastroenterology 52:1305–1312

    PubMed  CAS  Google Scholar 

  • Kuhler T, Swanson M, Shcherbuchin V, Larsson H, Mellgard B, Sjostrom JE (1998) Structure–activity relationship of 2-[[(2-pyridyl)methyl]thio]-1H-benzimidazoles as anti-Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy. J Med Chem 41:1777–1788

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Brea M, Domingo D, Sanchez I, Alarcon T (1997) Evolution of resistance to metronidazole and clarithromycin in Helicobacter pylori clinical isolates from Spain. J Antimicrob Chemother 40:279–281

    Article  PubMed  CAS  Google Scholar 

  • Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 16:1311–1315

    Article  Google Scholar 

  • Mirzaei J, Siavoshi F, Emami S, Safari F, Khoshayand MR, Shafiee A, Foroumadi A (2007) Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl]thiomorpholines and related compounds. Eur J Med Chem. doi:10.1016/j.ejmech.2007.11.019

  • Sachs G, Weeks DL, Wen Y, Marcus EA, Scott DR, Melchers K (2005) Acid acclimation by Helicobacter pylori. Physiology (Bethesda) 20:429–438

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Islamshahr Young Researchers Club, Islamic Azad University, and the Iran National Sciences Foundation (INSF).

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Authors and Affiliations

  1. Islamshahr Young Researchers Club, Department of Chemistry, Islamic Azad University, Islamshahr-Branch, Tehran, Iran

    Negar Mohammadhosseini & Bahram Letafat

  2. Microbiology Department, Faculty of Sciences, University of Tehran, Tehran, Iran

    Farideh Siavoshi & Fatemeh Safari

  3. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Saeed Emami

  4. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 14174, Iran

    Abbas Shafiee & Alireza Foroumadi

Authors
  1. Negar Mohammadhosseini
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  2. Bahram Letafat
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  3. Farideh Siavoshi
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  4. Saeed Emami
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  5. Fatemeh Safari
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  6. Abbas Shafiee
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  7. Alireza Foroumadi
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Correspondence to Alireza Foroumadi.

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Mohammadhosseini, N., Letafat, B., Siavoshi, F. et al. Synthesis and in vitro anti-Helicobacter pylori activity of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles. Med Chem Res 17, 578–586 (2008). https://doi.org/10.1007/s00044-008-9099-y

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  • DOI: https://doi.org/10.1007/s00044-008-9099-y

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