Effect of Fusaric Acid (A Dopamine Β‐hydroxylase Inhibitor) on Phaeochromocytoma

Nagasaka, Akio; Hara, Iwao; Imai, Yasuo; Uchikawa, T.; Yamauchi, Kei; Suzuki, Shigehiko; Takatsuki, K; Tomita, Akio; Niinomi, M.; Nakagawa, Hachiro; Itatsu, Takeharu; Hidaka, Hiroyoshi

doi:10.1111/j.1365-2265.1985.tb00142.x

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…The antithyroid and melanoma targeting properties of TU have been related to its inhibitory effects on distinct enzymatic activities, including thyroid iodide peroxidase [25], myeloperoxidase, eosinophil peroxidase [26] and tyrosinase [27]. Our finding that TU is also a selective inhibitor of nNOS preventing BH 4 ‐dependent dimerisation discloses a hitherto unrecognised property of this drug of potential relevance to the mechanism of the antithyroid action, in view of the recent demonstration of NOS activity in the thyroid gland [28].…”

Section: Discussionmentioning

confidence: 70%

2‐Thiouracil is a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin‐dependent enzyme activation and dimerisation

2000

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2-Thiouracil (TU), an established antithyroid drug and melanoma-seeker, was found to selectively inhibit neuronal nitric oxide synthase (nNOS) in a competitive manner (K i = 20 W WM), being inactive on the other NOS isoforms. The drug apparently interfered with the substrate-and tetrahydrobiopterin (BH 4 )-binding to the enzyme. It caused a 60% inhibition of H 2 O 2 production in the absence of L-arginine and BH 4 , and antagonised BH 4 -induced dimerisation of nNOS, but did not affect cytochrome c reduction. These results open new perspectives in the understanding of the antithyroid action of TU and provide a new lead structure for the development of selective nNOS inhibitors to elucidate the interdependence of the substrate and pteridine sites and to modulate pathologically aberrant NO formation. ß

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Section: Discussionmentioning

confidence: 70%

2‐Thiouracil is a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin‐dependent enzyme activation and dimerisation

2000

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“…It is also reported from species of Fusarium [42] and Gibberella fugikuroi [40]. Moreover, previous studies also show that it inhibits dopamine beta-hydroxylase enzymes that convert dopamine to norepinephrine and inhibits cell proliferation and DNA synthesis [41] anti-tumour activity on heme enzymes [40]. Structure-activity co-relation indicates that 2-pyridine carboxylic acid and its derivatives act as a bidentate chelating agent that effectively chelates metals in metal-containing protein complexes and enzymes required for growth replication or in ammatory response and thereby used to treat cancer.…”

Section: Discussionmentioning

confidence: 85%

“…5-butyl-2-pyridine carboxylic acid and its structure-function relations 5-butyl-2-pyridine carboxylic acid (also known as Fusaric acid, FA or 5-butyl-2-picolinic acid) and its analogues exhibited moderate antimicrobial activities [39], including growth inhibitors of E. coli [40], and act as quorum sensing [41]. It is also reported from species of Fusarium [42] and Gibberella fugikuroi [40].…”

Section: Discussionmentioning

confidence: 99%

Production and Characterization of Novel Board-spectrum Antimicrobial 5-butyl-2-pyridine carboxylic acid from Aspergillus fumigatus nHF-01

Mandal

Ghosh

Mitra

et al. 2022

Preprint

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Objectives: The present study aims to report on the production optimization, purification, and characterization of structural and functional attributes of a novel broad-spectrum antibacterial compound produced by Aspergillus fumigatus nHF-01 (GenBank Ac. No. MN190286).Materials and Methods: The culture conditions were optimized by using rigorous culture-set preparation considering various abiotic and biotic factors for a higher amount of antimicrobial production. The produced antimicrobial was solvent extracted and purified by preparative TLC and HPLC methods followed by characterization using UV-Vis, FT-IR, ESI-MS, and 1H-NMR spectroscopy. The MIC and MBC of the antimicrobials were determined against a set of Gram-positive and Gram-negative human pathogenic bacteria. The mode of action on cellular morphology and integrity were determined by LDH and SEM studies. Its biofilm-inhibition properties and synergistic activity with antibiotics were studied. The possible cytotoxic effect on human cell lines was also tested by MTT assay. The putative target site of action was evaluated through in silico molecular docking study. Results: The micro-fungus A. fumigatus nHF-01 produced the maximum antibacterial compound while grown in a combination of 2% MEB (w/v) and 4% YE (w/v) at pH 6.0 and 20 °C temperature with 100 rpm agitation for ten days. The DCM extractable crude compound has a potent growth inhibition against the target human food and topical pathogenic bacteria at a 15 mg/ml concentration and is stable up to 100 °C. The spectroscopic studies confirmed the antimicrobial compound as 5-butyl-2-pyridine carboxylic acid with MIC values from 0.069±0.0034 to 1.12±0.052 mg/ml and from 8.925±0.39 to 17.85±0.78 mg/ml; and MBC values from 8.925±0.40 to 17.85±0.776 mg/ml and from 0.069±0.0034 to 0.139±0.0065 mg/ml against human pathogenic Gram-positive and Gram-negative bacteria, respectively. A concentration of 0.139 and 17.85 mg/ml decreased the viability sharply within 15 min of the incubation period with the gradual increase in LDH activity, indicating a robust bactericidal and lytic mode of action. The time-kill kinetics study shows that at a 17.85 mg/ml dose (i.e. MBC), the compound caused zero viability of E. coli and S. epidermidis cells from the initial log CFU/ml 5.78 after 15 h of treatment. It caused a remarkable change in morphology like the formation of blebbing, notch, rupture of the entire cell walls, and entire dissolution of cell integrity at a concentration of 4 µg/ml and 129 µg/ml. It had cytotoxicity against the tested human lung carcinoma A549 cell line. It showed a notable antibiofilm activity at 20 µg/ml and 4 µg/ml comparable to the standard antibiofilm drug usnic acid 10 µg/ml and 64 µg/ml against E. coli and B. cereus. It had a synergistic activity with streptomycin, whereas ciprofloxacin and vancomycin showed additive effects. It showed the highest binding affinities with Quinol-Fumarate Reductase (1l0v), a respiratory enzyme. Conclusion: Thus, the above findings can be concluded that the strain A. fumigatus nHF-01 produces a novel broad-spectrum antimicrobial compound 5-butyl-2-pyridine carboxylic acid with potent bactericidal activity against human food and topical pathogenic bacteria. This is the first report of such a compound from the A. fumigatus.

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“…Within chemistry, interest has centred on their hydrogen bonding capability which has enabled sensing of anions, self‐assembly, and organocatalysis, for example. The thiourea functional group has been used widely in medicine, with 2‐thiouracil itself used to treat thyroid disorders for some time . Thioureas are investigated as antiviral agents, including non‐nucleoside HIV‐1 reverse transcriptase inhibitors, insecticidal growth regulators, anti‐inflammatory, and anticancer drugs .…”

Section: Methodsmentioning

confidence: 99%

Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging

et al. 2019

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Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. Iridium complexes present new opportunities for drug development and imaging in terms of structure and photoactivity. We have systematically synthesised a set of thiourea and guanidine compounds and iridium complexes thereof, and elucidated structure–activity relationships for cellular toxicity in three ovarian cancer cell lines and their cisplatin‐resistant sub‐lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea‐, guanidine‐, and iridium‐based materials.

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Effect of Fusaric Acid (A Dopamine Β‐hydroxylase Inhibitor) on Phaeochromocytoma

Cited by 9 publications

References 10 publications

2‐Thiouracil is a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin‐dependent enzyme activation and dimerisation

2‐Thiouracil is a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin‐dependent enzyme activation and dimerisation

Production and Characterization of Novel Board-spectrum Antimicrobial 5-butyl-2-pyridine carboxylic acid from Aspergillus fumigatus nHF-01

Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging

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