Medicinal Chemistry Research

, Volume 26, Issue 1, pp 93–100 | Cite as

TNF-α and IL-6 inhibitory effects of cyclic dipeptides isolated from marine bacteria Streptomyces sp

  • Yedukondalu Nalli
  • Shilpa Gupta
  • Vidushi Khajuria
  • Varun P. Singh
  • Mehak Sajgotra
  • Zabeer Ahmed
  • Narsinh L. Thakur
  • Asif AliEmail author
Original Research


Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. The anti-inflammatory cytokines are a series of immune regulatory molecules that control the pro inflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. The aim of the present study is to probe the anti-inflammatory potential of the crude extract and the bioactive metabolite isolated from marine bacteria Streptomyces sp. on key inflammatory mediators like tumor necrosis factor-α and interleukin-6. Here, we isolated ten known pyrazine-1,4-dione substituted cyclic dipeptide by semi-preparative HPLC and studied their anti-inflammatory activities against tumor necrosis factor-α and interleukin-6. Compound 3, 4, 5, 7 and 8 showed good inhibition of the both the cytokines in lipopolysaccharide-stimulated macrophages. The study reveal that compound 7 was to be specific inhibitor for tumor necrosis factor-α which efficiently inhibited tumor necrosis factor-α release in a dose-dependent manner and decreased lipopolysaccharide induced tumor necrosis factor-α production in human peripheral blood mononuclear cells in both the in vitro and in vivo experiments.


TNF-α IL-6 Streptomyces sp Cyclic dipeptides 



The authors are grateful to the University grant commission (UGC-New Delhi) and CSIR for providing financial support having the Grant No. ITR-0001 for the work of YN, and SM. YK, SG and VK acknowledge AcSIR for their enrolment in Ph. D program. VK also acknowledge DST for INSPIRE Fellowship. We are also thankful to Deeαpika Singh for recording the NMR experiments.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2016_1730_MOESM1_ESM.docx (6 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yedukondalu Nalli
    • 1
    • 2
  • Shilpa Gupta
    • 2
    • 3
  • Vidushi Khajuria
    • 2
    • 3
  • Varun P. Singh
    • 4
  • Mehak Sajgotra
    • 1
    • 2
  • Zabeer Ahmed
    • 2
    • 3
  • Narsinh L. Thakur
    • 5
  • Asif Ali
    • 1
    • 2
    Email author
  1. 1.Natural Product Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammu- TawiIndia
  2. 2.Academy of Scientific and Innovative ResearchCSIR-Indian Institute of MedicineJammu-TawiIndia
  3. 3.Inflammation Pharmacology DivisionCSIR-Indian Institute of Integrative MedicineJammu-TawiIndia
  4. 4.Medicinal Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  5. 5.Chemical Oceanography DivisionCSIR-National Institute of OceanographyGoaIndia

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