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香豆素衍生物作为抗利什曼原虫剂的生物活性

Biological Activity of Coumarin Derivatives as Anti-Leishmanial Agents.

作者信息

Mandlik Vineetha, Patil Sohan, Bopanna Ramanamurthy, Basu Sudipta, Singh Shailza

机构信息

National Centre for Cell Science, NCCS Complex, SP Pune University Campus, Ganeshkhind, Pune, India.

Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, Pashan, Pune, India.

出版信息

PLoS One. 2016 Oct 21;11(10):e0164585. doi: 10.1371/journal.pone.0164585. eCollection 2016.

DOI:10.1371/journal.pone.0164585
PMID:27768694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5074534/
Abstract

Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually. Treatment of this disease is difficult due to lack of appropriate medication and the growing problem of drug resistance. Natural compounds such as coumarins serve as complementary therapeutic agents in addition to the current treatment modalities. In this study, we have performed an in-silico screening of the coumarin derivatives and their anti-leishmanial properties has been explored both in-vitro and in-vivo. One of the compounds (compound 2) exhibited leishmanicidal activity and to further study its properties, nanoliposomal formulation of the compound was developed. Treatment of cutaneous lesions in BALB/c mice with compound 2 showed significantly reduced lesion size as compared to the untreated mice (p<0.05) suggesting that compound 2 may possess anti-leishmanial properties.

摘要

皮肤利什曼病每年影响近70万至130万人。由于缺乏合适的药物以及耐药性问题日益严重，这种疾病的治疗很困难。除了目前的治疗方式外，香豆素等天然化合物可作为辅助治疗剂。在本研究中，我们对香豆素衍生物进行了计算机模拟筛选，并在体外和体内探索了它们的抗利什曼原虫特性。其中一种化合物（化合物2）表现出杀利什曼原虫活性，为进一步研究其特性，开发了该化合物的纳米脂质体制剂。与未治疗的小鼠相比，用化合物2治疗BALB/c小鼠的皮肤损伤显示损伤大小显著减小（p<0.05），这表明化合物2可能具有抗利什曼原虫特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/14ae5cdb6a66/pone.0164585.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/8c0ce178f97c/pone.0164585.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/76ada517caa5/pone.0164585.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/b7c0c89073c4/pone.0164585.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/708b77aaca0b/pone.0164585.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/483f70552d7b/pone.0164585.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/14ae5cdb6a66/pone.0164585.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/8c0ce178f97c/pone.0164585.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/76ada517caa5/pone.0164585.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/b7c0c89073c4/pone.0164585.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/708b77aaca0b/pone.0164585.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/483f70552d7b/pone.0164585.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb5/5074534/14ae5cdb6a66/pone.0164585.g006.jpg

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本文引用的文献

[1]
Unraveling the Alkaline Phosphatase Inhibition, Anticancer, and Antileishmanial Potential of Coumarin-Triazolothiadiazine Hybrids: Design, Synthesis, and Molecular Docking Analysis.

Arch Pharm (Weinheim). 2016-7

[2]
Anti-Leishmania Activity of Osthole.

Pharmacognosy Res. 2016-3

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Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction.

Bioorg Med Chem Lett. 2016-2-1

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ACS Appl Mater Interfaces. 2015-4-3

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Molecules. 2014-8-28

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Biomed Res Int. 2014

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Eur J Pharm Biopharm. 2013-11

[8]
Iridoid glucosides from Nyctanthes arbortristis result in increased reactive oxygen species and cellular redox homeostasis imbalance in Leishmania parasite.

Eur J Med Chem. 2012-5-2

[9]
Use of antimony in the treatment of leishmaniasis: current status and future directions.

Mol Biol Int. 2011

[10]
Miltefosine-induced apoptotic cell death on Leishmania major and L. tropica strains.

Korean J Parasitol. 2011-3

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