Design, synthesis and antibacterial activity of novel andrographolide derivatives

Wang, Zhongli; Yu, Pei; Zhang, Gaoxiao; Xu, Li; Wang, Dingyuan; Wang, Liang; Zeng, Xiang‐Ping; Wang, Yuqiang

doi:10.1016/j.bmc.2010.04.094

Cited by 39 publications

(22 citation statements)

References 24 publications

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“…S2B), suggesting that the ␣,␤-unsaturated ␥-lactones and the covalent protein binding of Andro are critical to its anti-cancer property. Previous structure-activity relationship studies suggested that the ester derivative of Andro at the C14 hydroxyl group did not affect the C12-C13 moiety or the drug's potency (35)(36)(37). Therefore, we introduced an alkyne handle using the ester linkage at the C14 position to synthesize the clickable probe P1 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A Quantitative Chemical Proteomics Approach to Profile the Specific Cellular Targets of Andrographolide, a Promising Anticancer Agent That Suppresses Tumor Metastasis

Wang

Tan

Nguyễn

et al. 2014

Molecular & Cellular Proteomics

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Drug target identification is a critical step toward understanding the mechanism of action of a drug, which can help one improve the drug's current therapeutic regime and expand the drug's therapeutic potential. However, current in vitro affinity-chromatography-based and in vivo activity-based protein profiling approaches generally face difficulties in discriminating specific drug targets from nonspecific ones. Here we describe a novel approach combining isobaric tags for relative and absolute quantitation with clickable activity-based protein profiling to specifically and comprehensively identify the protein targets of andrographolide (Andro), a natural product with known anti-inflammation and anti-cancer effects, in live cancer cells. We identified a spectrum of specific targets of Andro, which furthered our understanding of the mechanism of action of the drug. Our findings, validated through cell migration and invasion assays, showed that Andro has a potential novel application as a tumor metastasis inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with a combination of drug analog synthesis, protein engineering, and mass-spectrometry-based approaches and determined the drugbinding sites of two protein targets, NF-B and actin. Molecular & Cellular Proteomics 13: 10.1074/mcp. M113.029793, 876-886, 2014.As most drugs exert pharmacological effects by interacting with their target proteins, the identification of these target proteins is a critical step in unraveling the mechanisms of drug action. It is also imperative for our understanding of the pharmacodynamics of a known drug, suggesting potentially unrevealed actions and thus refining future clinical applications of the substance. Traditional approaches used to identify protein targets of a drug typically utilize immobilized drug affinity chromatography coupled with mass spectrometry (MS) 1 (1, 2). These methods can be applied to cell lysates, but not in an in vivo setting, because of the requirement of a solid support. In vitro target profiling might not accurately reflect the drug's actions in the in vivo physiological environment. To overcome this limitation, several groups have used activity-based protein profiling (ABPP) combined with bio-orthogonal click chemistry to identify drug targets both in vitro and in vivo (supplemental Fig. S1) (3-15). ABPP probes exert their functions via covalent reactions with the target proteins or photoaffinity-based labeling via the incorporation of photoreactive groups. With the increasing sensitivity of modern MS platforms, low-abundance protein targets can be successfully identified. Although both conventional affinity chromatography and recent ABPP-based methods allow us to detect a set of candidate protein targets for a drug, it remains difficult to 1 The abbreviations used are: MS, mass spectrometry; ABPP, activity-based protein profiling; ICABPP, clickable activity-based protein profiling; iTRAQ, isobaric tags for relative and absolute quantitation; DMSO, dimethyl sulfoxide; Andro, androgr...

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Section: Resultsmentioning

confidence: 99%

A Quantitative Chemical Proteomics Approach to Profile the Specific Cellular Targets of Andrographolide, a Promising Anticancer Agent That Suppresses Tumor Metastasis

Wang

Tan

Nguyễn

et al. 2014

Molecular & Cellular Proteomics

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“…Many scholars have studied its antibacterial activity in vitro, and found its weak antibacterial activity, and found that andrographolide's clinical curative effects were achieved by other means. These means include inhibiting the bacteria virulence (Wang et al, 2010;Jiang et al,2009;Li et al, 2006), or reducing the damage of bronchial epithelial cells, or improving immunity function (Yan et al, 2013).…”

Section: Discussionmentioning

confidence: 98%

Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt

Xia

Chen³

et al. 2014

European Journal of Pharmacology

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“…This natural resource has been underexploited for the search of lead antimicrobial metabolites although there are numerous reports of plants being used as antimicrobial agents in traditional Ayurvedic medicine [37], Chinese medicine [38], and even in western Herbal medicine [39] as plants are capable of acting against bacteria and fungi because of their self-protection strategy in their environment [40]. To find out lead compounds responsible for antiinfective activities, there are a large number of research studies going on worldwide on traditional medicinal plants.…”

Section: Plant-derived Antimicrobial Secondary Metabolitesmentioning

confidence: 99%

Antimicrobial Secondary Metabolites—Extraction, Isolation, Identification, and Bioassay

Rahman

2015

Evidence-Based Validation of Herbal Medicine

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Design, synthesis and antibacterial activity of novel andrographolide derivatives

Cited by 39 publications

References 24 publications

A Quantitative Chemical Proteomics Approach to Profile the Specific Cellular Targets of Andrographolide, a Promising Anticancer Agent That Suppresses Tumor Metastasis

A Quantitative Chemical Proteomics Approach to Profile the Specific Cellular Targets of Andrographolide, a Promising Anticancer Agent That Suppresses Tumor Metastasis

Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt

Antimicrobial Secondary Metabolites—Extraction, Isolation, Identification, and Bioassay

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