Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α

Muhammad Raza Shah, Mohammad Arfan, Hazrat Amin, Zahid Hussain, Muhammad Irfan Qadir, M. Iqbal Choudhary, Donald Vanderveer, Osman Mesaik Mohammed Ahmed Hassan, Samreen Soomro, Almas Jabeen, Inam Ullah Khan

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst assay. Bergenin was isolated from the crude extract of Mallotus philippenensis after repeated column chromatography and was then subjected to chemical derivatization. The structures of all compounds were elucidated by NMR and mass spectroscopic techniques. Compound 2 was also studied using single crystal X-ray diffraction. Compounds 4, (54.5 ± 2.2%) 5 (47.5 ± 0.5%) 5, and 15 (86.8 ± 1.9%) showed significant (P ≤ 0.005) NO inhibitory activities whereas 6, 7, 11, 12 and 13 displayed moderate inhibitory activities that ranges between 16% and 31%. Furthermore compounds 4 and 15, were discovered as significant (P ≤ 0.005) TNF-α inhibitors with 98% and 96% inhibition, respectively, while compounds 3, 5, 7, 8, 11, and 12 showed low level of TNF-α inhibition (0.4-28%). Compounds 8, 13 and 15 exhibited moderate anti-inflammatory IC 50 activities with 212, 222, and 253 μM, respectively, compared to the standard anti-inflammatory drug indomethacin as well as the parent bergenin compound. No cytotoxic effects could be detected when the compounds were tested on 3T3 cells up to concentrations of 100 μM.

Original languageEnglish
Pages (from-to)2744-2747
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number8
DOIs
Publication statusPublished - 15 Apr 2012
Externally publishedYes

Fingerprint

Derivatives
Anti-Inflammatory Agents
Isocoumarins
3T3 Cells
Column chromatography
Respiratory Burst
Cyclooxygenase 2
Biological Products
Complex Mixtures
Interleukin-1
X-Ray Diffraction
Indomethacin
Chromatography
Weight Loss
Assays
Norepinephrine
Fats
Maintenance
Nuclear magnetic resonance
Single crystals

Keywords

  • Anti-inflammatory activity
  • Bergenin derivatives
  • Cytotoxicity, NO and TNF-α inhibitory activity
  • Neutrophil respiratory burst activity
  • X-ray diffraction analysis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Shah, M. R., Arfan, M., Amin, H., Hussain, Z., Qadir, M. I., Iqbal Choudhary, M., ... Khan, I. U. (2012). Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α. Bioorganic and Medicinal Chemistry Letters, 22(8), 2744-2747. https://doi.org/10.1016/j.bmcl.2012.02.096

Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α. / Shah, Muhammad Raza; Arfan, Mohammad; Amin, Hazrat; Hussain, Zahid; Qadir, Muhammad Irfan; Iqbal Choudhary, M.; Vanderveer, Donald; Mohammed Ahmed Hassan, Osman Mesaik; Soomro, Samreen; Jabeen, Almas; Khan, Inam Ullah.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 8, 15.04.2012, p. 2744-2747.

Research output: Contribution to journalArticle

Shah, MR, Arfan, M, Amin, H, Hussain, Z, Qadir, MI, Iqbal Choudhary, M, Vanderveer, D, Mohammed Ahmed Hassan, OM, Soomro, S, Jabeen, A & Khan, IU 2012, 'Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 8, pp. 2744-2747. https://doi.org/10.1016/j.bmcl.2012.02.096
Shah, Muhammad Raza ; Arfan, Mohammad ; Amin, Hazrat ; Hussain, Zahid ; Qadir, Muhammad Irfan ; Iqbal Choudhary, M. ; Vanderveer, Donald ; Mohammed Ahmed Hassan, Osman Mesaik ; Soomro, Samreen ; Jabeen, Almas ; Khan, Inam Ullah. / Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 8. pp. 2744-2747.
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