The Herbicidally Active Compound N-2-(6-Methyl-Pyridyl)-Aminomethylene Bisphosphonic Acid Inhibits In Vivo Aromatic Biosynthesis

1999 ◽  
Vol 18 (2) ◽  
pp. 73-79 ◽  
Author(s):  
G. Forlani ◽  
B. Lejczak ◽  
P. Kafarski
Keyword(s):  
Active Compound ◽  
Bisphosphonic Acid ◽  
Aromatic Biosynthesis

scholarly journals The herbicidally active compound N-2-(5-chloro-pyridyl) aminomethylene bisphosphonic acid acts by inhibiting both glutamine and aromatic amino acid biosynthesis

2000 ◽  
Vol 27 (7) ◽  
pp. 677 ◽  
Author(s):  
Giuseppe Forlani ◽  
Barbara Lejczak ◽  
Pawel Kafarski
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Active Compound ◽  
Cultured Cells ◽  
Shikimate Pathway ◽  
Glutamate Synthase ◽  
Phenylalanine Level ◽  
Bisphosphonic Acid

The effect of the herbicidally active compound N-2-(5-chloro-pyridyl)aminomethylene bisphosphonic acid (Cl-pyr-AMBPA), previously found in vitro to inhibit the activity of the first enzyme in the shikimate pathway 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, was investigated in vivo on suspension cultured cells of Nicotiana plumbaginifolia Viviani. Amino acid pool measurement showed an actual reduction of tyrosine, tryptophan and phenylalanine level following the addition of the compound to the growth medium. However, an even stronger effect was noticed for other amino acids, mainly glutamine. When the activity of the enzymes involved in the glutamate cycle was measured in the presence of Cl-pyr-AMBPA, glutamate synthase was unaffected, while glutamine synthetase was significantly inhibited. Contrary to the herbicide phosphinothricin, the inhibitor bound reversibly to the enzyme. Kinetic analysis accounted for an inhibition of uncompetitive type with respect to ammonium, glutamate and ATP, withKivalues of 113, 97 and 39 M, respectively. Only the exogenous supply of a mixture of glutamine and aromatic amino acids relieved cell growth inhibition, suggesting that the phytotoxic properties of Cl-pyr-AMBPA are due to inhibition of key enzymes in both the corresponding pathways.

scholarly journals In VitroInhibitory and Cytotoxic Activity of MFM 501, a Novel Codonopsinine Derivative, against Methicillin-ResistantStaphylococcus aureusClinical Isolates

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Saiful Azmi Johari ◽  
Mastura Mohtar ◽  
Sharifah Aminah Syed Mohammad ◽  
Rohana Sahdan ◽  
Zurina Shaameri ◽  
...  
Keyword(s):  
Active Compound ◽  
Inhibitory Activity ◽  
Normal Cell ◽  
Bactericidal Effect ◽  
Selectivity Index ◽  
Cytotoxicity Activity ◽  
A Value ◽  
Value Determination ◽  
Mic Value

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel ofS. aureusisolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55S. aureusisolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58S. aureusisolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for furtherin vivoinvestigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.

scholarly journals New Tetrahydroacridine Hybrids with Dichlorobenzoic Acid Moiety Demonstrating Multifunctional Potential for the Treatment of Alzheimer’s Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 3765
Author(s):  
Kamila Czarnecka ◽  
Małgorzata Girek ◽  
Przemysław Wójtowicz ◽  
Paweł Kręcisz ◽  
Robert Skibiński ◽  
...  
Keyword(s):  
Active Compound ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Free Radical Scavenger ◽  
Neuroprotective Activity ◽  
Radical Scavenger ◽  
Catalytic Active Site ◽  
Aβ Aggregation ◽  
Ic50 Values

A series of new tetrahydroacridine and 3,5-dichlorobenzoic acid hybrids with different spacers were designed, synthesized, and evaluated for their ability to inhibit both cholinesterase enzymes. Compounds 3a, 3b, 3f, and 3g exhibited selective butyrylcholinesterase (EqBuChE) inhibition with IC50 values ranging from 24 to 607 nM. Among them, compound 3b was the most active (IC50 = 24 nM). Additionally, 3c (IC50 for EeAChE = 25 nM and IC50 for EqBuChE = 123 nM) displayed dual cholinesterase inhibitory activity and was the most active compound against acetylcholinesterase (AChE). Active compound 3c was also tested for the ability to inhibit Aβ aggregation. Theoretical physicochemical properties of the compounds were calculated using ACD Labs Percepta and Chemaxon. A Lineweaver–Burk plot and docking study showed that 3c targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, 3c appears to possess neuroprotective activity and could be considered a free-radical scavenger. In addition, 3c did not cause DNA damage and was found to be less toxic than tacrine after oral administration; it also demonstrated little inhibitory activity towards hyaluronidase (HYAL), which may indicate that it possesses anti-inflammatory properties. The screening for new in vivo interactions between 3c and known receptors was realized by yeast three-hybrid technology (Y3H).

In Vitro Investigation of Anti-Diabetic Effect of Taxus cuspidate Extracts by Ultrasound Assisted Method

2012 ◽  
Vol 40 (06) ◽  
pp. 1205-1215 ◽  
Author(s):  
Linda Xiao ◽  
Wei-Guo Lao ◽  
Yi Tan ◽  
Xianqin Qu
Keyword(s):  
Glucose Uptake ◽  
Active Compound ◽  
Medicinal Herbs ◽  
Chinese Medicinal Herbs ◽  
Active Components ◽  
In Vitro Investigation ◽  
Ultrasound Assisted ◽  
Taxus Cuspidate

Extracting active components from Chinese medicinal herbs efficiently is a key step in the investigation of their pharmacological effects and modes of action. In this project, we compared the ultrasound-assisted method and the conventional solvent method for extracting the active compound of Taxus cuspidate (dong bei hong dou shan). Through the analysis of various extractions with a quadruple time-of-fight (Q-TOF) LC/MS, we demonstrated that the ultrasound-assisted method reduced solvent consumption and had shorter extraction time, while the extraction yields of the active compound (taxol) were equivalent to or even higher than those obtained with the conventional solvent extraction method. Through the comparison of Taxus cuspidate extracts (TCEs) with different concentrations of acetone and ethanol, we proved that 50% ethanol was an optimal solvent for extracting taxol from Taxus cuspidate. Based on traditional Chinese medicine (TCM) literature, we further determined whether TCEs possess antidiabetic effects by testing glucose uptake in 3T3-L1 adipocytes treated with TCEs from Taxus cuspidate bark and twigs under insulin stimulation (100 nM). The results showed that neither taxol (10 μg/ml) nor TCEs (1 and 0.1 mg/ml) changed glucose uptake significantly compared with insulin alone. This study demonstrated that the ultrasound-assisted method with 50% ethanol is a highly efficient approach for extracting Taxus cuspidate, which may be applicable for extraction of other Chinese medicinal herbs. Extracts of Taxus cuspidate bark and twigs had no effect on insulin stimulated-glucose uptake in vitro. This result conflicts with the description in TCM literature. Further in vivo study to clarify Taxus cuspidate's metabolic actions is necessary.

scholarly journals Development of a Fluorescent Assay to Search New Drugs Using Stable tdTomato-Leishmania, and the Selection of Galangin as a Candidate With Anti-Leishmanial Activity

2021 ◽  
Vol 11 ◽  
Author(s):  
María Fernanda García-Bustos ◽  
Agustín Moya Álvarez ◽  
Cecilia Pérez Brandan ◽  
Cecilia Parodi ◽  
Andrea Mabel Sosa ◽  
...  
Keyword(s):  
Active Compound ◽  
Wild Strain ◽  
Fluorescence Assay ◽  
New Drugs ◽  
Lipid Inclusion ◽  
Screening Assay ◽  
Meglumine Antimoniate ◽  
Wide Range

Antimonials continue to be considered the first-line treatment for leishmaniases, but its use entails a wide range of side effects and serious reactions. The search of new drugs requires the development of methods more sensitive and faster than the conventional ones. We developed and validated a fluorescence assay based in the expression of tdTomato protein by Leishmania, and we applied this method to evaluate the activity in vitro of flavonoids and reference drugs. The pIR1SAT/tdTomato was constructed and integrated into the genome of Leishmania (Leishmania) amazonensis. Parasites were selected with nourseothricin (NTC). The relation of L. amaz/tc3 fluorescence and the number of parasites was determined; then the growth in vitro and infectivity in BALB/c mice was characterized. To validate the fluorescence assay, the efficacy of miltefosine and meglumine antimoniate was compared with the conventional methods. After that, the method was used to assess in vitro the activity of flavonoids; and the mechanism of action of the most active compound was evaluated by transmission electron microscopy and ELISA. A linear correlation was observed between the emission of fluorescence of L. amaz/tc3 and the number of parasites (r2 = 0.98), and the fluorescence was stable in the absence of NTC. No differences were observed in terms of infectivity between L. amaz/tc3 and wild strain. The efficacy of miltefosine and meglumine antimoniate determined by the fluorescence assay and the microscopic test showed no differences, however, in vivo the fluorescence assay was more sensitive than limiting dilution assay. Screening assay revealed that the flavonoid galangin (GAL) was the most active compound with IC50 values of 53.09 µM and 20.59 µM in promastigotes and intracellular amastigotes, respectively. Furthermore, GAL induced mitochondrial swelling, lipid inclusion bodies and vacuolization in promastigotes; and up-modulated the production of IL-12 p70 in infected macrophages. The fluorescence assay is a useful tool to assess the anti-leishmanial activity of new compounds. However, the assay has some limitations in the macrophage-amastigote model that might be related with an interfere of flavanol aglycones with the fluorescence readout of tdTomato. Finally, GAL is a promising candidate for the development of new treatment against the leishmaniasis.

scholarly journals Exploring the mechanism of the anti-hypertension properties of Morinda citrifolia through a bioinformatics approach

2021 ◽  
Vol 48 (3) ◽  
Author(s):  
Dian Laila Purwaningroom ◽  
◽  
Sholihatul Maghfirah ◽  
Muhaimin Rifai ◽  
Widodo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Active Compound ◽  
Ace Inhibitor ◽  
Methanol Extract ◽  
Bioinformatic Analysis ◽  
Morinda Citrifolia ◽  
Dependent Manner ◽  
Active Compounds

Traditionally, noni (Morinda citrifolia L.) has been used to treat hypertension in tropical countries. The noni extract was proven to reduce blood pressure and relatively safe to the liver and kidney in the animal model. This extract could inhibit angiotensin-converting enzyme (ACE) and plays a pivotal role in controlling blood pressure. However, the active compound of the extract that has function as the ACE inhibitor is still unknown. Therefore, the objective of this study was to examine the mechanism of anti-hypertension of noni methanol extract as well as its active compound that acts as the ACE inhibitor by using a bioinformatics approach. An enzyme activity analysis showed that noni methanol extract inhibits ACE activity based on a dose-dependent manner. Further analysis using bioinformatic analysis suggested that three active compounds of Morinda citrifolia, namely linoleic acid, palmitate, and oleic acid, might be bound to PPARA and NOS3 protein. The two targeted protein is predicted as a regulator of blood pressure through the PPARA pathway. The findings showed that M. citrifolia has numerous active compounds containing multiple protein targets, which regulate blood pressure. However, in vitro and in vivo research should be conducted to provide evidence for the mechanism.

scholarly journals Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hwayong Park ◽  
Kwang Hoon Song ◽  
Pil Mun Jung ◽  
Ji-Eun Kim ◽  
Hyunju Ro ◽  
...  
Keyword(s):  
Active Compound ◽  
Gene Promoter ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Melanin Content ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plantArctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content inα-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

scholarly journals Antiparasitic Efficacy of Herbal Extracts and Active Compound Against Gyrodactylus kobayashii in Carassius auratus

2021 ◽  
Vol 8 ◽  
Author(s):  
Shun Zhou ◽  
Jing Dong ◽  
Yongtao Liu ◽  
Qiuhong Yang ◽  
Ning Xu ◽  
...  
Keyword(s):  
Active Compound ◽  
Carassius Auratus ◽  
Herbal Medicines ◽  
Optimal Choice ◽  
Economic Losses ◽  
High Concentration ◽  
Antiparasitic Activity ◽  
Short Time

Gyrodactylus spp. Nordmann, 1832 (Monogenea: Gyrodactylidae) are common ectoparasites of teleost fishes. Infection with these parasites can increase the mortality of fish and cause considerable economic losses in intensive aquaculture. To find an effective antiparasitic agent for the control of gyrodactylosis, antiparasitic efficacy of crude extracts of 36 herbal medicines was evaluated using a Carassius auratus (Cypriniformes, Cyprinidae)—Gyrodactylus kobayashii model. Among all tested medicines, methanol extract of Dioscorea collettii var. hypoglauca (Dioscoreales, Dioscoreaceae) was the most efficient, with an EC50 value of 4.17 mg/L. This extract showed 100% antiparasitic efficacy against G. kobayashii at 10 mg/L and had a therapeutic index (TI, LC50/EC50) of 5.26, which is higher than that of formaldehyde (TI = 4.58), a widely used parasiticide in aquaculture. Subsequently, the potential mechanism of antiparasitic activity of dioscin, an active compound isolated from D. collettii var. hypoglauca was investigated and the histopathological alterations in goldfish after exposure to dioscin were also studied. The in vivo trial indicated dioscin showed significant antiparasitic activity with a 24 h-EC50 value of 1.58 mg/L and it exhibited 100% antiparasitic efficacy at 0.6 mg/L. Also, G. kobayashii could be completely removed in vivo within 2 h at 0.6 mg/L dioscin. Whereas, mean survival time of this worm in vitro was 4.99 h, and some individuals even reached 12 h at the same concentration of dioscin. These results indicated that 0.6 mg/L of dioscin did not completely kill all worms within 2 h, but just temporarily remove the worms from goldfish. Scanning electron microscopy (SEM) analysis showed that most of the microvilli on the tegument surface of G. kobayashii dropped after exposure to dioscin. This might be one of the potential mechanisms of antiparasitic activity of dioscin against G. kobayashii. Furthermore, no severe histopathological alteration was observed after exposure to a high concentration of dioscin for a short time. Considering both effectiveness and safety, therapeutic baths with a high concentration of dioscin for a short time might be a more optimal choice for the treatment of gyrodactylosis in aquaculture.

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