Characterization of 7-amino-4-methylcoumarin as an effective antitubercular agent: structure–activity relationships

Tandon, R. P.; Ponnan, Prija; Aggarwal, Neha; Pathak, Rakesh; Baghel, Anil Singh; Gupta, Garima; Arya, Amit; Nath, Mahendra; Parmar, Virinder S.; Raj, Hanumantharao G.; Prasad, Ashok K.; Bose, Mridula

doi:10.1093/jac/dkr355

Cited by 35 publications

(21 citation statements)

References 35 publications

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“…Similar observations were previously reported for M . tuberculosis that was treated with isoniazid or other compounds that target mycolic acids 26, 27 . These effects of IMB-YH-8 on cell wall and cell morphology are in agreement with the function of its target PknB in controlling cell shape and regulating cell wall synthesis that requires mycolic acids 6, 28, 29 .…”

Section: Discussionmentioning

confidence: 99%

A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity

Wang

Zhou

et al. 2017

Sci Rep

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Protein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. Here, we identified and characterized a novel small molecule compound named IMB-YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8 inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a dose-dependent manner. The compound did not inhibit human Akt1 or other serine/threonine kinases in M. tuberculosis except for the highly homologous PknA. IMB-YH-8 bound to PknB with a moderate affinity. Molecular docking revealed that IMB-YH-8 interacts with the catalytic domain of PknB. Observations of electron microscopy showed that IMB-YH-8 changed the morphology of H37Rv and disrupted the cell wall. The differential transcriptional response of M. tuberculosis to IMB-YH-8 revealed changes in SigH regulatory pathways modulated by PknB. Notably IMB-YH-8 not only potently inhibited drug-sensitive and multidrug-resistant clinical isolates but also exhibited a dose dependent inhibition of intracellular M. tuberculosis. Taken together, these in vitro data demonstrate that IMB-YH-8 is a novel inhibitor of PknB, which potently prevents growth of M. tuberculosis. It is as yet unclear whether inhibition of PknA contributes to the anti-tubercular action of IMB-YH-8.

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Section: Discussionmentioning

confidence: 99%

A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity

Wang

Zhou

et al. 2017

Sci Rep

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“…YX-28 isolated from Ginkgo biloba L. may be used as natural preservative in food (Liu et al 2008). AMC also exhibited maximum antitubercular activity, with MIC of 1 mg L −1 against M. tuberculosis when produced by synthetic pathway (Tandon et al 2011).…”

Section: Ascomycetes Fungimentioning

confidence: 99%

Fungi as a source of natural coumarins production

Costa

Tavares

Oliveira

2016

Appl Microbiol Biotechnol

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Natural coumarins and derivatives are compounds that occur naturally in several organisms (plant, bacteria, and fungi) consisting of fused benzene and α-pyrone rings. These compounds show high technological potential applications in agrochemical, food, pharmaceuticals, and cosmetics industries. Therefore, the need for bulk production of coumarins and the advancement of the chemical and pharmaceutical industries led to the development of synthetic coumarin. However, biotransformation process, synthetic bioengineering, metabolic engineering, and bioinformatics have proven effective in the production of natural products. Today, these biological systems are recognized as green chemistry innovation and business strategy. This review article aims to report the potential of fungi for synthesis of coumarin. These microorganisms are described as a source of natural products capable of synthesizing many bioactive metabolites. The features, classification, properties, and industrial applications of natural coumarins as well as new molecules obtained by basidiomycetes and ascomycetes fungi are reported in order to explore a topic not yet discussed in the scientific literature.

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“…In addition, the current anti-tuberculosis drugs induce various/serious side effects including hepatotoxicity, ototoxicity, and nephrotoxicity. In this aspect, as one of feasible alternatives for overcoming limitations of the drug's side effects, particularly, including rifampicin, isoniazid, ethambutol and moxifloxacin, various studies for developing anti-tuberculosis drugs were reported from active substances derived from traditional diverse medicinal plants and biological resources [19][20][21][22][23]. However, antituberculosis agents of effective/safe next-generation that can be utilized or used as potential/novel first-line anti-tuberculosis drugs, particularly, the extracts, natural products, and/or semi-synthetic compounds, have not yet been reported in the global pharmaceutical market.…”

Section: Discussionmentioning

confidence: 99%

The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents

Choi¹,

Lee²

2016

Asian Pacific Journal of Tropical Biomedicine

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A B S T R A C T Objective: To evaluate the anti-mycobacterial activity of Melia azedarach L. (M. azedarach) and Lobelia chinensis Lour. (L. chinensis) extracts against the growth of Mycobacterium tuberculosis (M. tuberculosis). Methods: The anti-M. tuberculosis activity of M. azedarach and L. chinensis extracts were evaluated using different indicator methods such as resazurin microtiter assay (REMA) and mycobacteria growth indicator tube (MGIT) 960 system assay. The M. tuberculosis was incubated with various concentrations (50-800 mg/mL) of the extracts for 5 days in the REMA, and for 4 weeks in MGIT 960 system assay. Results: M. azedarach and L. chinensis extracts showed their anti-M. tuberculosis activity by strongly inhibiting the growth of M. tuberculosis in a concentration-dependent manner in the REMA and the MGIT 960 system assay. Particularly, the methanol extract of M. azedarach and n-hexane extract of L. chinensis consistently exhibited their effects by effectively inhibiting the growth of M. tuberculosis in MGIT 960 system for 4 weeks with a single-treatment, indicating higher anti-M. tuberculosis activity than other extracts,and their minimum inhibitory concentrations were measured as 400 mg/mL and 800 mg/ mL, respectively. Conclusions: These results demonstrate that M. azedarach and L. chinensis extracts not only have unique anti-M. tuberculosis activity, but also induce the selective anti-M. tuberculosis effects by consistently inhibiting or blocking the growth of M. tuberculosis through a new pharmacological action. Therefore, this study suggests the potential of them as effective candidate agents of next-generation for developing a new anti-tuberculosis drug, as well as the advantage for utilizing traditional medicinal plants as one of effective strategies against tuberculosis.

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Characterization of 7-amino-4-methylcoumarin as an effective antitubercular agent: structure–activity relationships

Abstract: The present study clearly demonstrated the in vitro antitubercular potential of the novel drug candidate NA5. Further studies are warranted to establish the in vivo efficacy and therapeutic potential of NA5.

Cited by 35 publications

References 35 publications

A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity

A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity

Fungi as a source of natural coumarins production

The anti-tubercular activity of Melia azedarach L. and Lobelia chinensis Lour. and their potential as effective anti-Mycobacterium tuberculosis candidate agents

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