Antitubercular Constituents from the Roots of<i>Engelhardia roxburghiana</i>

Lin, Wen Yu; Cf, Peng; Tsai, Ian‐Lih; Chen, Jih Jung; Cheng, Ming‐Jen; Chen, Ih Sheng

doi:10.1055/s-2005-837786

Cited by 44 publications

(19 citation statements)

References 15 publications

(16 reference statements)

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“…The engelhardione analogs 1a - c and their corresponding methyl ether derivatives 4a - c only showed marginal antibacterial activities. Unfortunately, both the originally published structure 17 ( 1a ) of engelhardione and pterocarine ( 1b ) only showed weak antituberculosis activity (200 μg ml −1 ) in our assay. These results are consistent with a recent report by Reddy and co-workers that corniculatolides, close structural lactone analogs of engelhardione/pterocarine diarylheptanoids, did not inhibit the growth of M. tuberculosis at 100 μg ml −1 .…”

Section: Resultsmentioning

confidence: 63%

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Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Shen¹,

Maddox²,

Adhikari³

et al. 2013

J Antibiot

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The natural product engelhardione is an underexplored chemotype for developing novel treatments for bacterial infections; we therefore explored this natural product scaffold for chemical diversification and structure-activity relationship studies. Macrocyclic engelhardione and structural regioisomers were synthesized using a series of aldol condensations and selective hydrogenations to generate the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether analogs. An extended macrocyclic chemical library was then produced by oxime formation, reductive amination, and O-alkylation. Antibacterial evaluation revealed that the reductive amination derivatives 7b and 7d showed moderate activities (minimum inhibitory concentrations: 12.5-25 μg ml−1) against Mycobacterium tuberculosis and Gram-positive pathogens, as well as anti-Gram-negative activity against an efflux impaired E. coli strain. These results provide validated leads for further optimization and development.

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Section: Resultsmentioning

confidence: 63%

“…One such example, engelhardione was recently isolated from the roots of Engelhardia roxburghiana and reported to show potent antituberculosis activity with a minimum inhibitory concentration (MIC) of 0.2 μg ml −1 . 17 …”

Section: Introductionmentioning

confidence: 99%

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Shen¹,

Maddox²,

Adhikari³

et al. 2013

J Antibiot

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show abstract

“…1 It belongs to a broad family of natural plant metabolites called diarylheptanoids, which are characterized by two phenolic aromatic rings linked by a linear seven-carbon aliphatic ketone chain to form a macrocyclic architecture. 2 The macrocyclic diphenyl ether moiety is widely present in many naturally occurring molecules, including vancomycin, K-13, aceroside IV, piperazinomycin, and engelhardione (Fig.…”

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confidence: 99%

Total synthesis and structural revision of engelhardione

Shen

Sun

2011

Tetrahedron Letters

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The total synthesis of the macrocyclic natural product engelhardione is reported. This effort led to the structural revision of the published structure of engelhardione to that of pterocarine. The revision reflects the change of the substitution pattern of one phenyl ether ring from the meta to the para position. To confirm, pterocarine (2) and its close regioisomer 3 were subsequently synthesized for comparison. Moreover, to the best of our knowledge, our synthesis of 1 represents the first example of a 14-membered macrocyclic diarylheptanoid with a meta-meta substitution pattern at the diphenyl ether moiety.

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“…In addition, three pharmacophoric regions, aromatic hydrocarbon (AroC), hydrogen bond acceptor (HAc), and hydrogen bond donor (HDr), were also discovered in this ligand. Lin et al (2005) 3 Berberine N Hydrastis canadensis Gentry et al (1998) 4 Pilocarpine N Pilocarpus racemosa Rastogi et al (1998) 5 Pinostrobin N Teloxys graveolens Camacho-Corona et al (2009) 6 Voacangine N Tabernaemontana citrifolia Rastogi et al (1998) Cryptolepine HCl (Ligand 7) is an important lead obtained via virtual screening, molecular docking, and pharmacophore analysis. Cryptolepine HCl is an indoloquinoline alkaloid obtained from the West African medicinal plant Cryptolepis sanguinolenta (Gibbons et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Interactome analysis and design of inhibitors against selected protein targets of Ser/Thr protein kinase (STPK) signaling pathways in Mycobacterium tuberculosis H37Rv

et al. 2015

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ABSTRACT. Tuberculosis continues to be a major cause of mortality worldwide despite significant advances in chemotherapy and development of the BCG vaccine. Although curable, the tuberculosis treatment period (6-9 months) presents many concerns, including patient noncompliance and the development of drug toxicity and drug resistance. This study aimed to understand the protein-protein interactions of key proteins involved in the Mycobacterium tuberculosis STPK signal transduction pathway (such as PknB, PknE, and PstP); in addition, we attempted to identify promising leads for the inhibition of protein-protein interactions. Interactome analyses revealed the interactions of these protein targets with several other proteins, including PknG and PbpA. Drug-like candidates were screened based on Lipinski's rule of five and the absorption digestion metabolism (2015) excretion toxicity. Molecular docking of the target proteins with the selected ligands identified cryptolepine HCl to be a common molecule interacting with all protein targets (with a good docking score). The generation of a pharmacophore model for cryptolepine HCl revealed three pharmacophoric regions: aromatic hydrocarbon, hydrogen bond acceptor, and hydrogen bond donor, which play important roles in its interaction with the protein targets. Therefore, cryptolepine HCl appears to be a promising drug candidate for further optimization and validation against M. tuberculosis.

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Antitubercular Constituents from the Roots ofEngelhardia roxburghiana

Cited by 44 publications

References 15 publications

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Total synthesis and structural revision of engelhardione

Interactome analysis and design of inhibitors against selected protein targets of Ser/Thr protein kinase (STPK) signaling pathways in Mycobacterium tuberculosis H37Rv

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