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绿色合成双香豆素衍生物,意外获得强效抗菌和抗炎剂。

Green, unexpected synthesis of bis-coumarin derivatives as potent anti-bacterial and anti-inflammatory agents.

作者信息

Chougala Bahubali M, Samundeeswari S, Holiyachi Megharaja, Naik Nirmala S, Shastri Lokesh A, Dodamani Suneel, Jalalpure Sunil, Dixit Sheshagiri R, Joshi Shrinivas D, Sunagar Vinay A

机构信息

Department of Chemistry, Karnatak University, Dharwad, 580 003, Karnataka, India.

Department of Chemistry, Karnatak University, Dharwad, 580 003, Karnataka, India.

出版信息

Eur J Med Chem. 2018 Jan 1;143:1744-1756. doi: 10.1016/j.ejmech.2017.10.072. Epub 2017 Oct 28.

Abstract

A green and efficient protocol has been developed and a series of coumarin based pyrano[3,2-c]chromene derivatives (2) have been synthesized using multi-component reaction (MCR) approach. Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (3) and C-C chromenes (5) have been isolated instead of expected product 4 by the reaction of compound (2) in formic acid at 90 °C for about 4-5 h and at 130 °C for about 8-10 h respectively. Further, C-Cchromenes (5) formation was confirmed by intramolecular cyclization of compounds (3). These compounds were screened for their biological activities and most of them exhibited promising antibacterial activity. The anti-inflammatory assay was evaluated against HRBC membrane stabilization method and the compounds exhibit excellent anti-inflammatory activity. Molecular docking study has been performed for all the synthesized compounds with Klebsiella pneumoni aeacetolactate synthase and results obtained are quite promising.

摘要

已开发出一种绿色高效的方法,并采用多组分反应(MCR)方法合成了一系列基于香豆素的吡喃并[3,2-c]色烯衍生物(2)。通过将化合物(2)分别在90℃下于甲酸中反应约4-5小时以及在130℃下反应约8-10小时,意外地分离出了3-香豆素基-3-吡唑基丙酸(3)和C-C色烯(5),而不是预期产物4。此外,通过化合物(3)的分子内环化证实了C-C色烯(5)的形成。对这些化合物进行了生物活性筛选,其中大多数表现出有前景的抗菌活性。采用HRBC膜稳定法评估了其抗炎活性,这些化合物表现出优异的抗炎活性。对所有合成化合物与肺炎克雷伯菌乙酰乳酸合酶进行了分子对接研究,所得结果很有前景。

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