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水杨酸偶联异恶唑啉类似物的合成及对免疫细胞增殖和血管生成的生物评价。

Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis.

机构信息

Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore, 570005 Karnataka, India; Department of Chemistry, JSS College of Arts, Commerce & Science, Ooty Road, Mysore, 570025, India.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga, 577203, Karnataka, India.

出版信息

Eur J Med Chem. 2016 May 23;114:153-61. doi: 10.1016/j.ejmech.2016.02.052. Epub 2016 Feb 24.

Abstract

Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compound's effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future.

摘要

有丝分裂原性是指天然或合成化合物诱导细胞分裂或增殖的能力。本文合成了一系列含有异恶唑啉结构的水杨酸衍生物(8a-j),并评估了它们针对淋巴细胞增殖和血管生成的免疫药理学活性。在体外实验中,用人类外周血淋巴细胞和鼠脾细胞研究了 8a-j 化合物的有丝分裂原性。结果表明,在 8a-j 系列化合物中,化合物 8e 对人和鼠淋巴细胞均显示出强烈的增殖反应。化合物 8e 的增殖指数与参考有丝分裂原 Con A 相当,有丝分裂原性是由于 IL-2 分泌增加所致。还进行了体内 CAM 和大鼠角膜血管生成试验,以评估化合物对内皮细胞迁移和增殖的影响,这表明 8e 也诱导内皮细胞的增殖。该研究报告了新型有丝分裂原 8e 的合成免疫刺激和促血管生成活性,这可能在未来转化为新药。

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