Molecular and Cellular Biochemistry

, Volume 345, Issue 1–2, pp 69–76 | Cite as

Chemical modification of ascorbic acid and evaluation of its lipophilic derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity

  • Riyaz Mohamed
  • K. K. Dharmappa
  • Shaista Tarannum
  • N. M. Jameel
  • S. A. Kannum
  • H. S. Ashrafulla
  • Lokanath Rai
  • Cletus JMD’ Souza
  • M. A. Shekhar
  • Bannikuppe S. Vishwanath


The halo 6-fatty acid esters of l-ascorbic acid 3a, 3b and 6-fatty acid esters of l-ascorbic acid 5ag were achieved from l-ascorbic acid 1. Compounds 3a, 3b and 5ag were evaluated for anti-oxidant, anti-lipid peroxidation, and secretory phospholipase A2 (sPLA2) inhibition in vitro, and sPLA2 induced mouse paw edema. All the derivatives retained their anti-oxidant property compared to ascorbic acid at 6 × 10−4M and are good inhibitors of lipid peroxidation at 1 mg ml−1 as evaluated by 2, 2-Diphenyl-1-picrylhydrazyl radical and thio-barbituric acid methods, respectively. Compounds 5e and 5f significantly inhibited purified group I sPLA2 from Naja naja and group II sPLA2 from Vipera russelli, human synovial fluid and human pleural fluid with IC50 value ranging from 64 ± 1.95 to 82 ± 1.3 and 48 ± 2.27 to 61 ± 2.23 μM, respectively. The compounds 5e and 5f also showed varying degree of potency in neutralizing indirect hemolytic activity of sPLA2 at 50 μM concentration, and sPLA2 induced mouse paw edema at the dose 3 mg/kg. Further docking studies also confirmed that compounds 5e and 5f have maximum interaction with increasing negative energy value. Single molecule possessing both anti-oxidant and anti-inflammatory activities is of great therapeutic significance in inflammatory disorders.


6-fatty acid esters of l-ascorbic acid sPLA2 Anti-inflammatory activity Docking Anti-oxidant 



Author expresses his sincere gratitude to the Lady Tata Memorial Trust, Mumbai for financial assistance, and the University of Mysore, Mysore, for providing laboratory facilities. We extend our thanks to Dr. C R Nagendran, Professor (retired), Dept of Botany, University of Mysore for the needful help in english correction.

Supplementary material

11010_2010_561_MOESM1_ESM.doc (40 kb)
Supplementary material 1 (DOC 40 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Riyaz Mohamed
    • 1
  • K. K. Dharmappa
    • 1
  • Shaista Tarannum
    • 1
  • N. M. Jameel
    • 2
  • S. A. Kannum
    • 3
  • H. S. Ashrafulla
    • 4
  • Lokanath Rai
    • 5
  • Cletus JMD’ Souza
    • 1
  • M. A. Shekhar
    • 2
    • 6
  • Bannikuppe S. Vishwanath
    • 1
  1. 1.Department of Studies in BiochemistryUniversity of MysoreMysoreIndia
  2. 2.Chowdaiah Medical Centre and Apoorva Diabetes Foundation, Centre for Diabetes Care and ResearchMysoreIndia
  3. 3.Department of ChemistryYuvarajas collegeMysoreIndia
  4. 4.Volvox TechnologiesHassanIndia
  5. 5.Department of Studies in ChemistryUniversity of MysoreMysoreIndia
  6. 6.Department of EndocrinologyMysore Medical College and Research InstituteMysoreIndia

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