Department of Studies in Biochemistry, University of Mysore, Mysore, 570006, India.
Mol Cell Biochem. 2010 Dec;345(1-2):69-76. doi: 10.1007/s11010-010-0561-z. Epub 2010 Aug 22.
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 A(2) (sPLA(2)) inhibition in vitro, and sPLA(2) induced mouse paw edema. All the derivatives retained their anti-oxidant property compared to ascorbic acid at 6 × 10(-4)M 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 sPLA(2) from Naja naja and group II sPLA(2) 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 sPLA(2) at 50 μM concentration, and sPLA(2) 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.
L-抗坏血酸 3a、3b 的 6-脂肪酸酯和 L-抗坏血酸 5a-g 的 6-脂肪酸酯由 L-抗坏血酸 1 合成。对化合物 3a、3b 和 5a-g 进行了体外抗氧化、抗脂质过氧化和分泌型磷脂酶 A2（sPLA2）抑制活性评价，并进行了 sPLA2 诱导的小鼠足肿胀试验。与抗坏血酸相比，所有衍生物在 6×10(-4)M 时均保持抗氧化活性，在 1mg/ml 时通过 2,2-二苯基-1-苦基肼基和硫代巴比妥酸法分别评估为良好的脂质过氧化抑制剂。化合物 5e 和 5f 显著抑制了来自眼镜蛇和中华眼镜蛇的 I 型 sPLA2、人滑膜液和人胸腔液中的 II 型 sPLA2，IC50 值范围分别为 64±1.95 至 82±1.3 和 48±2.27 至 61±2.23μM。化合物 5e 和 5f 在 50μM 浓度下对 sPLA2 的间接溶血活性也具有不同程度的中和作用，在 3mg/kg 剂量下对 sPLA2 诱导的小鼠足肿胀也具有作用。进一步的对接研究也证实，化合物 5e 和 5f 与增加的负能值具有最大的相互作用。具有抗氧化和抗炎活性的单一分子在炎症性疾病中具有重要的治疗意义。
