scholarly journals In vitro evaluation of the effect of C-4 substitution on methylation of 7,8-dihydroxycoumarin: metabolic profile and catalytic kinetics

2018 ◽  
Vol 5 (1) ◽  
pp. 171271 ◽  
Author(s):  
Yang-Liu Xia ◽  
Tong-Yi Dou ◽  
Yong Liu ◽  
Ping Wang ◽  
Guang-Bo Ge ◽  
...  
Keyword(s):  
Structural Modification ◽  
Metabolic Stability ◽  
Electronic Effects ◽  
Pharmacological Activities ◽  
Oh Groups ◽  
Structural Modifications ◽  
Catalytic Kinetics ◽  
Relationship Of

Daphnetin (7,8-dihydroxycoumarin (7,8-DHC)) and its C-4 derivatives have multiple pharmacological activities, but the poor metabolic stability of these catechols has severely restricted their application in the clinic. Methylation plays important roles in catechol elimination, although thus far the effects of structural modifications on the metabolic selectivity and the catalytic efficacy of human catechol- O -methyltransferase (COMT) remain unclear. This study was aimed at exploring the structure–methylation relationship of daphnetin and its C-4 derivatives, including 4-methyl, 4-phenyl and 4-acetic acid daphnetin. It was achieved by identifying the methylated products generated and by careful characterization of the reaction kinetics. These catechols are selectively metabolized to the corresponding 8- O -methyl conjugates, and this regioselective methylation could be elucidated by flexible docking, in which all the 8-OH groups of these catechols are much closer than the 7-OH groups to catalytic residue LYS144 and methyl donor AdoMet. The results of the kinetic analyses revealed that the Cl int values of the compounds could be strongly affected by the C-4 substitutions, which could be partially explained by the electronic effects of the C-4 substituents and the coordination modes of 7,8- dihydroxycoumarins in the active site of COMT. These findings provide helpful guidance for further structural modification of 7,8-DHCs to improve metabolic stability.

scholarly journals Chemical Derivatization and Characterization of Novel Antitrypanosomals for African Trypanosomiasis

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4488
Author(s):  
Aboagye Kwarteng Dofuor ◽  
Temitayo Samson Ademolue ◽  
Cynthia Mmalebna Amisigo ◽  
Kwaku Kyeremeh ◽  
Theresa Manful Gwira
Keyword(s):  
Structural Modification ◽  
Spectroscopic Analysis ◽  
Microscopic Analysis ◽  
The Novel ◽  
Chemical Derivatization ◽  
African Trypanosomiasis ◽  
Chemical Structures ◽  
Normal Ratio

The search for novel antitrypanosomals and the investigation into their mode of action remain crucial due to the toxicity and resistance of commercially available antitrypanosomal drugs. In this study, two novel antitrypanosomals, tortodofuordioxamide (compound 2) and tortodofuorpyramide (compound 3), were chemically derived from the natural N-alkylamide tortozanthoxylamide (compound 1) through structural modification. The chemical structures of these compounds were confirmed through spectrometric and spectroscopic analysis, and their in vitro efficacy and possible mechanisms of action were, subsequently, investigated in Trypanosoma brucei (T. brucei), one of the causative species of African trypanosomiasis (AT). The novel compounds 2 and 3 displayed significant antitrypanosomal potencies in terms of half-maximal effective concentrations (EC50) and selectivity indices (SI) (compound 1, EC50 = 7.3 μM, SI = 29.5; compound 2, EC50 = 3.2 μM, SI = 91.3; compound 3, EC50 = 4.5 μM, SI = 69.9). Microscopic analysis indicated that at the EC50 values, the compounds resulted in the coiling and clumping of parasite subpopulations without significantly affecting the normal ratio of nuclei to kinetoplasts. In contrast to the animal antitrypanosomal drug diminazene, compounds 1, 2 and 3 exhibited antioxidant absorbance properties comparable to the standard antioxidant Trolox (Trolox, 0.11 A; diminazene, 0.50 A; compound 1, 0.10 A; compound 2, 0.09 A; compound 3, 0.11 A). The analysis of growth kinetics suggested that the compounds exhibited a relatively gradual but consistent growth inhibition of T. brucei at different concentrations. The results suggest that further pharmacological optimization of compounds 2 and 3 may facilitate their development into novel AT chemotherapy.

scholarly journals Synthesis characterization and antibacterial studies of 4-aminoantipyrine schiff’s bases

2017 ◽  
Vol 2 (01) ◽  
pp. 8-14 ◽  
Author(s):  
K Sunand ◽  
K Vinay Kumar ◽  
K Ashwini ◽  
P Suresh Kumar ◽  
S Vishnu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Schiff Bases ◽  
Vital Role ◽  
Spectroscopic Techniques ◽  
Schiff’S Bases ◽  
Pharmacological Activities ◽  
Schiff's Bases ◽  
Ir Spectroscopic

Aim: To synthesize and evaluate 4-aminoantipyrine related schiff’s bases as antibacterial agents. Objective: To synthesize, purify, characterize and evaluate 4-aminoantipyrine. Method: Schiff bases derived from 4-aminoantipyrine play a vital role in biological and pharmacological activities. Knowing the importance of 4-aminoatipyrine schiff bases and their analogues wide varieties of bioactivities like analgesic, antiviral, antipyretic, anti-rheumatic, antimicrobial and anti-inflammatory activities have been widely studied. 4-aminoantipyrine compounds C1 (anisaldehyde), C2 (p-hydroxybenzaldehyde) and C3(vanillin) were prepared by condensation between 4-amino antipyrine and substituted aromatic benzaldehydes. The products were purified by recrystallization by using ethanol, characterized by IR spectroscopy. The N-H stretching in 4-aminoantipyrine is shown at 3430 cm-1 and -3325 cm-1. The -HC=N- stretching is observed in the range of 1508-1504 cm-1 The –OCH3 stretching is found at 1888 cm-1. 4-amino antipyrine related schiff’s bases evaluated their activity as antimicrobials in-vitro by spread plate method against E.coli. Schiff bases have potent antibacterial activity with gram negative bacteria E.coli. Results: Synthesis and characterization of a schiff bases derived from substituted benzaldehydes and 4-aminoantipyrine was evaluated and characterized with the IR spectroscopic techniques and schiff bases have shown potent antibacterial activity against E.Coli.

Scanning Studies of Cell Surfaces

1973 ◽  
Vol 31 ◽  
pp. 608-609
Author(s):  
Virginia Fonte ◽  
Nancy Weller ◽  
Keith R. Porter
Keyword(s):  
Cell Cycle ◽  
Structural Organization ◽  
Cell Surfaces ◽  
Detailed Characterization ◽  
A Cell ◽  
Relationship Of ◽  
The Relationship ◽  
Scanning Electron

The surfaces of a cell in its topography and anti-genicity expresses subtle variations in the effective genome, as well as the physiology and structural organization of the underlying cytoplasm. Understanding the relationship of these various factors to the surface depends in part on obtaining a detailed characterization of the topography of cells and how this topography changes with phases in the cell cycle, with transformation to malignancy and with the cell's response to such physiologically active agents as cyclic AMP.We have therefore explored the usefulness of the scanning electron microscope in investigations of the cell's topography. Cells grown under favourable in vitro conditions have been fixed in glutaraldehyde, dehydrated in acetone and dried by the critical point method of Anderson.

Aurones as New Porcine Pancreatic α-Amylase Inhibitors

2019 ◽  
Vol 16 (3) ◽  
pp. 333-340
Author(s):  
Khashayar Roshanzamir ◽  
Elaheh Kashani-Amin ◽  
Azadeh Ebrahim-Habibi ◽  
Latifeh Navidpour
Keyword(s):  
Biological Activities ◽  
Structural Isomers ◽  
Structural Requirements ◽  
Oh Groups ◽  
Structure Activity ◽  
Inhibitory Activities ◽  
Pharmacological Potential ◽  
Relationship Of ◽  
Amylase Inhibitors

Background: Aurones, (Z)-2-benzylidenebenzofuran-3-one derivatives, are naturallyoccurring structural isomers of flavones, with promising pharmacological potential. </P><P> Methods: In this study, the structural requirements for the inhibition of porcine pancreatic &#945;- amylase by hydroxylated or methoxylated aurone derivatives were investigated by assessing their in vitro biological activities against porcine pancreatic &#945;-amylase. </P><P> Results: The structure-activity relationship of these inhibitors based on both in vitro and in silico findings showed that the hydrogen bonds between the OH groups of the A or B ring of (Z)- benzylidenebenzofuran-3-one derivatives and the catalytic residues of the binding site are crucial for their inhibitory activities. </P><P> Conclusion: It seems that the OH groups in aurones inhibit &#945;-amylase in a manner similar to that of OH groups in flavones and flavonols.

Enhanced Solubility and Permeability of Salicis cortex Extract by Formulating as a Microemulsion

Planta Medica ◽  
2018 ◽  
Vol 84 (12/13) ◽  
pp. 976-984 ◽  
Author(s):  
Vieri Piazzini ◽  
Elisabetta Bigagli ◽  
Cristina Luceri ◽  
Anna Rita Bilia ◽  
Maria Camilla Bergonzi
Keyword(s):  
In Vitro Digestion ◽  
Oral Formulation ◽  
Tween 20 ◽  
Array Detector ◽  
Microemulsion System ◽  
Pharmacological Activities ◽  
Enhanced Solubility ◽  
Permeability Assay

AbstractA microemulsion system was developed and investigated as a novel oral formulation to increase the solubility and absorption of Salicis cortex extract. This extract possesses many pharmacological activities, in particular, it is beneficial for back pain and osteoarthritic and rheumatic complaints. In this work, after qualitative and quantitative characterization of the extract and the validation of an HPLC/diode array detector analytical method, solubility studies were performed to choose the best components for microemulsion formulation. The optimized microemulsion consisted of 2.5 g of triacetin, as the oil phase, 2.5 g of Tween 20 as the surfactant, 2.5 g of labrasol as the cosurfactant, and 5 g of water. The microemulsion was visually checked, characterized by light scattering techniques and morphological observations. The developed formulation appeared transparent, the droplet size was around 40 nm, and the ζ-potential result was negative. The maximum loading content of Salicis cortex extract resulted in 40 mg/mL. Furthermore, storage stability studies and an in vitro digestion assay were performed. The advantages offered by microemulsion were evaluated in vitro using artificial membranes and cells, i.e., parallel artificial membrane permeability assay and a Caco-2 model. Both studies proved that the microemulsion was successful in enhancing the permeation of extract compounds, so it could be useful to ameliorate the bioefficacy of Salicis cortex.

scholarly journals Metabolic Stability and Metabolite Characterization of Capilliposide B and Capilliposide C by LC–QTRAP–MS/MS

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 178 ◽  
Author(s):  
Zhongzhe Cheng ◽  
Xing Zhou ◽  
Zhifeng Du ◽  
Wenyi Li ◽  
Bingying Hu ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Species Difference ◽  
Liver Microsomes ◽  
Metabolic Stability ◽  
Rat Liver Microsomes ◽  
Triterpenoid Saponins ◽  
Additional Information

Capilliposide B (LC-B) and Capilliposide C (LC-C), two new triterpenoid saponins extracted from Lysimachia capillipes Hemsl, exhibit potential anticancer activity both in vitro and in vivo. However, their metabolic process remains unclear. In this study, the metabolic stability of LC-B, LC-C, and Capilliposide A (LC-A, a bioactive metabolite of LC-B and LC-C) was investigated in human, rat, and mouse liver microsomes, respectively. Thereafter, their metabolites were identified and characterized after oral administration in mice. As a result, species difference was found in the metabolic stability of LC-B and LC-C. All three compounds of interest were stable in human and rat liver microsomes, but LC-B and LC-C significantly degraded in mouse liver microsomes. The metabolic instability of LC-B and LC-C was mainly caused by esterolysis. Moreover, 19 metabolites were identified and characterized in mouse biological matrices. LC-B and LC-C mainly underwent deglycosylation and esterolysis, accompanied by dehydration, dehydrogenation, and hydroxylation as minor metabolic reactions. Finally, the metabolic pathway of LC-B and LC-C in mice was proposed. Our results updated the preclinical metabolism and disposition process of LC-B and LC-C, which provided additional information for better understanding efficacy and safety.

Intergrainular structure and deformation mechanism in nanocrystalline materials

1995 ◽  
Vol 53 ◽  
pp. 192-193
Author(s):  
H.Q. Ye ◽  
P.H. Ping ◽  
D.X. Li ◽  
J.Y. Huang ◽  
Y.K. Wu
Keyword(s):  
Deformation Mechanism ◽  
Structural Modification ◽  
Boundary Structure ◽  
X Ray Diffraction ◽  
Gas Condensation ◽  
Average Grain Size ◽  
Relationship Of ◽  
Structure Properties

It is recognized that boundary structure (GB) characterization is essential in order to understand the structure-properties relationship of nanocrystalline (NC). In most cases, NC materials have to suffer deformation during compacting or ball milling techniques, a deep and systematic study on deformation mechanism is also necessary. In this paper, characterization of microstructure in NC materials synthesized by three methods has been presented.1. Ordered and Disordered Regions at GBs of NC Pd The NC Pd samples were synthesized by the inert gas condensation and in situ compacting technique. The results of X-ray diffraction and HREM observations showed that the average grain size of the NC Pd is about 10 nm. It can be seen that most of the GBs have ordered structure and no 'gas-like' feature has been observed. Some disordered GB regions, such as nanovoid formed during compacting process, are also detected as marked by "V" in Fig.l. The structural modification from the disordered state was found during in situ HREM investigation.

Monoclonal antibodies that detect differentiation surface antigens on human myelomonocytic cells

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 382-392 ◽  
Author(s):  
B Perussia ◽  
G Trinchieri ◽  
D Lebman ◽  
J Jankiewicz ◽  
B Lange ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Bone Marrow Cells ◽  
Human Peripheral Blood ◽  
In Vitro Study ◽  
Antigenic Determinants ◽  
Monocytic Cells ◽  
Relationship Of ◽  
Differentiation Pathways

Abstract We describe here the production and characterization of several new monoclonal antibodies that recognize differentiation antigens present on human cells of the myelomonocytic lineage. The lineage and the stage specificities of our reagents (myeloid-, monocytic-, and myelomonocytic- specific) were determined on the basis of their reactivity with human cell lines and with human peripheral blood and bone marrow cells. Cross- competition experiments demonstrated that some of the antibodies react with the same or closely associated antigenic determinants. Five antigens have been identified in this way: one present on myeloid, one on monocytic, and three on both myeloid and monocytic cells. The possible relationship of our antibodies with other established monoclonal antibodies is discussed, in addition to their use in the in vitro study of the differentiation pathways of human hemopoietic cells and in the characterization of leukemias.

scholarly journals Methyl jasmonate promote protostane triterpenes accumulation by up-regulating the expression of squalene epoxidases in Alisma orientale

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rong Tian ◽  
Wei Gu ◽  
Yuchen Gu ◽  
Chao Geng ◽  
Fei Xu ◽  
...  
Keyword(s):  
Squalene Epoxidase ◽  
Enzyme Assays ◽  
Pharmacological Activities ◽  
E Coli ◽  
Meja Treatment ◽  
Alisma Orientale ◽  
Rate Limiting ◽  
Triterpene Biosynthesis

AbstractProtostane triterpenes, which are found in Alisma orientale, are tetracyclic triterpenes with distinctive pharmacological activities. The natural distribution of protostane triterpenes is limited mainly to members of the botanical family Alismataceae. Squalene epoxidase (SE) is the key rate-limiting enzyme in triterpene biosynthesis. In this study, we report the characterization of two SEs from A. orientale. AoSE1 and AoSE2 were expressed as fusion proteins in E. coli, and the purified proteins were used in functional research. In vitro enzyme assays showed that AoSE1 and AoSE2 catalyze the formation of oxidosqualene from squalene. Immunoassays revealed that the tubers contain the highest levels of AoSE1 and AoSE2. After MeJA induction, which is the main elicitor of triterpene biosynthesis, the contents of 2,3-oxidosqualene and alisol B 23-acetate increased by 1.96- and 2.53-fold, respectively. In addition, the expression of both AoSE proteins was significantly increased at four days after MeJA treatment. The contents of 2,3-oxidosqualene and alisol B 23-acetate were also positively correlated with AoSEs expression at different times after MeJA treatment. These results suggest that AoSE1 and AoSE2 are the key regulatory points in protostane triterpenes biosynthesis, and that MeJA regulates the biosynthesis of these compounds by increasing the expression of AoSE1 and AoSE2.

scholarly journals Synthesis and Characterization of Substituted Starch Grafted Methyl Nadic Anhydride and Substituted with 4-Aminoantipyrine

2019 ◽  
pp. 103-113
Author(s):  
Firyal M. Ali ◽  
Mohammed A. Farhan
Keyword(s):  
Structural Modification ◽  
In Vitro Study ◽  
Extended Period ◽  
Controlled Drug Release ◽  
Controlled Delivery ◽  
Ceric Ammonium Nitrate ◽  
Grafted Copolymer ◽  
Zero Time

In this research the structural modification of starch was carried out with methyl nadic anhydride (M1) as a spacer by using ceric ammonium nitrate (CAN) as an initiator, and grafted copolymer was substituted with amino drug such as 4-aminoantipyrine (M1B), this design of carries for controlled delivery of therapeutic agent which could release the entrapped drug over an extended period of time, due to its nontoxic, biodegradable and slow digesting nature, the new drug copolymer was characterized by FTIR, 1H-NMR and UV Spectroscopes. The prepared drug copolymer was analyzed in different pH values at (37°C) as in vitro study and controlled drug release was compared at zero time and after four days.

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