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

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The halo 6-fatty acid esters of l-ascorbic acid 3a, 3b and 6-fatty acid esters of l-ascorbic acid 5a-g were achieved from l-ascorbic acid 1. Compounds 3a, 3b and 5a-g 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 IC 50 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.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume345
Issue number1-2
DOIs
StatePublished - Dec 1 2010

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Mohamed, R., Dharmappa, K. K., Tarannum, S., Jameel, N. M., Kannum, S. A., Ashrafulla, H. S., Rai, L., Souza, C. J., Shekhar, M. A., & Vishwanath, B. S. (2010). Chemical modification of ascorbic acid and evaluation of its lipophilic derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity. Molecular and Cellular Biochemistry, 345(1-2), 69-76. https://doi.org/10.1007/s11010-010-0561-z