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

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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 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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Studies in Biochemistry, University of Mysore, Mysore, 570006, India

    Riyaz Mohamed, K. K. Dharmappa, Shaista Tarannum, Cletus JMD’ Souza & Bannikuppe S. Vishwanath

  2. Chowdaiah Medical Centre and Apoorva Diabetes Foundation, Centre for Diabetes Care and Research, Saraswathipuram, Mysore, 570006, India

    N. M. Jameel & M. A. Shekhar

  3. Department of Chemistry, Yuvarajas college, Mysore, 570006, India

    S. A. Kannum

  4. Volvox Technologies, Channarayapatana, Hassan, 573116, India

    H. S. Ashrafulla

  5. Department of Studies in Chemistry, University of Mysore, Mysore, 570006, India

    Lokanath Rai

  6. Department of Endocrinology, Mysore Medical College and Research Institute, Mysore, 570001, India

    M. A. Shekhar

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  1. Riyaz Mohamed
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Correspondence to Bannikuppe S. Vishwanath.

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Mohamed, R., Dharmappa, K.K., Tarannum, S. et al. Chemical modification of ascorbic acid and evaluation of its lipophilic derivatives as inhibitors of secretory phospholipase A2 with anti-inflammatory activity. Mol Cell Biochem 345, 69–76 (2010). https://doi.org/10.1007/s11010-010-0561-z

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  • DOI: https://doi.org/10.1007/s11010-010-0561-z

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