Identifying Protein Kinase Inhibitors Using an Assay Based on Inhibition of Aerial Hyphae Formation in Streptomyces.

Waters, Barbara; Saxena, Geeta; Wanggui, Yangsheng; Kau, David A.; Wrigley, Stephen K.; Stokes, Richard W.; Davies, Julian

doi:10.7164/antibiotics.55.407

Cited by 56 publications

(80 citation statements)

References 34 publications

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“…4 Citrinin (2), a well-known mycotoxin, is both nephrotoxic 13 and carcinogenic. 25 It was reported to show moderate cytotoxicity against the mouse NS-1 cell line with LD 99 values of 25 mg mL -1 , 15 and antifungal activities against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and A. niger at a concentration of 100 mg/disk.…”

Section: Resultsmentioning

confidence: 99%

“…Mass spectra and highresolution mass spectra were taken with a BioTOF II ESI mass spectrometer. 1D and 2D NMR spectra were recorded in MeOH-d 4 and DMSO-d 6 on a Varian INOVA Unity (500 MHz) spectrometer. The chemical shift Chromatographic fractions and pure compounds were monitored by TLC, detected by absorption of UV light at 254 nm and a color reaction by spraying with a solution of 10%, v/v, sulfuric acid/EtOH followed by 5 min heating at 120 °C.…”

Section: General Proceduresmentioning

confidence: 99%

“…4 The mycelia fragments of Streptomyces were spread on minimal medium ISP 4 agar plates for the generation of a bacteria lawn. Compounds of known concentration dissolved in MeOH were dispensed onto disks in 20 mL aliquots.…”

Section: Hyphae Formation Inhibition Assaymentioning

confidence: 99%

“…It has been shown that a variety of kinase inhibitors block this process. 3,4 During the course of our search for novel protein kinase inhibitors from natural resources, [5][6][7][8][9][10] an acetonesoluble extract of the fungus Penicillium sp. H9318 showed inhibitory activity towards both mammalian protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) in an in vitro phosphatase assay.…”

Section: Introductionmentioning

confidence: 99%

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Citrinin derivatives from the soil filamentous fungus Penicillium sp. H9318

Yao¹,

Sebisubi²,

Voo³

et al. 2011

J. Braz. Chem. Soc.

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A investigação do extrato orgânico produzido na fermentação microbiológica de Penicillium sp. H9318 conduziu ao isolamento de um novo alcaloide isoquinolínico, o composto (5S)-3,4,5,7-tetrametil-5,8-di-hidróxi-6(5H)-isoquinolinona (1), juntamente com quatro outros conhecidos compostos derivados da citrinina (2-5). Uma atividade inibitória significativa no ensaio da inibição da formação dos halos (HFI), foi exibida pela citrinina (2), semelhante àquela observada pelo Streptomyces 85E, enquanto os compostos 1, 3, 4 e 5 não mostraram atividade inibitória com respeito ao ensaio HFI quando testados com 20 mg/disco. Em relação ao ensaio de citotoxicidade, a citrinina (2) demonstrou uma atividade inibitória mais fraca quando comparada as linhagens de células cancerosas MCF-7 (IC 50 71,93 µmol L -1 ), LNCaP (IC 50 77,92 µmol L -1 ), LU-1 (147,85 µmol L -1 ) e KB (IC 50 65,93 µmol L -1 ).Investigation of a microbial fermentation organic extract of Penicillium sp. H9318 led to the isolation of a new isoquinolinone alkaloid, (5S)-3,4,5,7-tetramethyl-5,8-dihydroxyl-6(5H)-isoquinolinone (1), along with four known citrinin derivatives (2-5). Citrinin (2) exhibited significant inhibitory activity against Streptomyces 85E in the hyphae formation inhibition (HFI) assay, while compounds 1, 3-5 were not active when tested at 20 mg/disk in the HFI assay. Citrinin (2) further demonstrated a weak inhibitory activity against MCF-7 (IC 50 71.93 µmol L -1 ), LNCaP (IC 50 77.92 µmol L -1 ), LU-1 (147.85 µmol L -1 ) and KB (IC 50 65.93 µmol L -1 ) cell lines, respectively, in the cytotoxicity assay.

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Section: Resultsmentioning

confidence: 99%

Section: General Proceduresmentioning

confidence: 99%

Section: Hyphae Formation Inhibition Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Citrinin derivatives from the soil filamentous fungus Penicillium sp. H9318

Yao¹,

Sebisubi²,

Voo³

et al. 2011

J. Braz. Chem. Soc.

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“…Together with the observed broad substrate specificity of PyrA, these findings provide opportunities to generate pyridomycin derivatives with novel or enhanced bioactivities by rational engineering of the biosynthetic pathway or combinatorial biosynthesis. Given its special molecular architecture (9,16), pyridomycin also offers an opportunity to discover new chemistry for natural product biosynthesis.…”

mentioning

confidence: 99%

Identification and Characterization of the Pyridomycin Biosynthetic Gene Cluster of Streptomyces pyridomyceticus NRRL B-2517

Huang

Wang

Yin

et al. 2011

Journal of Biological Chemistry

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Pyridomycin is a structurally unique antimycobacterial cyclodepsipeptide containing rare 3-(3-pyridyl)-L-alanine and 2-hydroxy-3-methylpent-2-enoic acid moieties. The biosynthetic gene cluster for pyridomycin has been cloned and identified from Streptomyces pyridomyceticus NRRL B-2517. Sequence analysis of a 42.5-kb DNA region revealed 26 putative open reading frames, including two nonribosomal peptide synthetase (NRPS) genes and a polyketide synthase gene. A special feature is the presence of a polyketide synthase-type ketoreductase domain embedded in an NRPS. Furthermore, we showed that PyrA functioned as an NRPS adenylation domain that activates 3-hydroxypicolinic acid and transfers it to a discrete peptidyl carrier protein, PyrU, which functions as a loading module that initiates pyridomycin biosynthesis in vivo and in vitro. PyrA could also activate other aromatic acids, generating three pyridomycin analogues in vivo.

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Biofabrication of iron oxide nanoparticles by leaf extract of Rhamnus virgata: Characterization and evaluation of cytotoxic, antimicrobial and antioxidant potentials

Abbasi

Iqbal

Mahmood

et al. 2019

Applied Organom Chemis

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In the present study, plant‐mediated synthesis of iron oxide nanoparticles (IONPs) using leaves extract of Rhamnus virgata (Roxb.) as a potential stabilizing, reducing and chelating agent is reported. The biogenic IONPs are extensively characterized for their physical and biological properties. The morphology, structure and physicochemical properties of biogenic IONPs were characterized using ultraviolet spectroscopy, X‐ray diffraction, Fourier transform‐infrared analysis, scanning electron microscopy, energy‐dispersive spectroscopy, transmission electron microscopy, Raman spectroscopy and dynamic light scattering. The Scherrer equation deduced a mean crystallite size of ~20 nm for IONPs. Detailed in vitro biological activities revealed significant therapeutic potentials for IONPs. Potential antibacterial and antifungal activities are reported for IONPs. Bioinspired IONPs have shown potential results against HepG2 cells (IC50: 13.47 μg/ml). Dose‐dependent cytotoxicity assays were revealed against Leishmania tropica (KMH23) promastigotes (IC50: 8.08 μg/ml) and amastigotes (IC50: 20.82 μg/ml) using different concentrations of IONPs (1–200 μg/ml). The cytotoxic activity was also studied using brine shrimps, and their IC50 value was calculated as 32.41 μg/ml. Significant antioxidant [TAC (51.4%), DPPH (79.4%) and total reducing power (62%)], protein kinase and alpha amylase inhibition assays were revealed. The biocompatibility assays using red blood cells (> 200 μg/ml) and macrophages (> 200 μg/ml) confirmed the biosafe nature of IONPs. In conclusion, bioinspired IONPs have shown potential biological applications and should be subjected to further research work to develop their nano‐pharmacological relevance in biomedical applications.

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Identifying Protein Kinase Inhibitors Using an Assay Based on Inhibition of Aerial Hyphae Formation in Streptomyces.

Cited by 56 publications

References 34 publications

Citrinin derivatives from the soil filamentous fungus Penicillium sp. H9318

Citrinin derivatives from the soil filamentous fungus Penicillium sp. H9318

Identification and Characterization of the Pyridomycin Biosynthetic Gene Cluster of Streptomyces pyridomyceticus NRRL B-2517

Biofabrication of iron oxide nanoparticles by leaf extract of Rhamnus virgata: Characterization and evaluation of cytotoxic, antimicrobial and antioxidant potentials

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