scholarly journals Characterization of Chloroquine-Ferriheme Solution Structure Using EXAFS and MD

2014 ◽  
Vol 70 (a1) ◽  
pp. C721-C721
Author(s):  
David Kuter ◽  
Victor Streltsov ◽  
Natalia Davydova ◽  
Gerhard Venter ◽  
Kevin Naidoo ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Solution Structure ◽  
Antimalarial Activity ◽  
Dimethyl Ester ◽  
Protoporphyrin Ix ◽  
Md Simulations ◽  
Exafs Spectrum ◽  
Convincing Evidence ◽  
The Other ◽  
Dimeric Form

The complex formed between the antimalarial drug chloroquine (CQ) and its target iron(III)protoporphyrin IX (ferriheme) in aqueous solution is of considerable importance in understanding its mechanism of antimalarial activity. Recently, convincing evidence showed that CQ induces the μ-oxo dimeric form of ferriheme in aqueous solution, but the structure of this complex in solution is uncertain.[1] Molecular dynamics (MD) simulations in aqueous solution were used to model the structure of μ-oxo ferriheme and two possible conformations of the CQ-ferriheme complex, one in which CQ π-stacked with the unligated face of ferriheme and the other in which CQ was docked between the porphyrin rings. The EXAFS spectrum of μ-oxo ferriheme obtained from frozen solution strongly supported the hydrated structure determined from MD simulation where an excellent fit to the spectrum was only obtained when incorporating waters of hydration at regions identified by computation. On the other hand, the EXAFS spectrum recorded on the dried solid of μ-oxo ferriheme required no solvating waters to produce excellent agreement with the crystal structure of μ-oxo ferrihaem dimethyl ester.[2] The EXAFS spectrum recorded on a frozen aqueous solution of the CQ-ferriheme complex was able to distinguish between the two conformations modeled computationally. Fits to the EXAFS spectrum using the π-stacked structure produced poor agreement while those obtained using the docked conformation reproduced the spectrum well. This indicated that the latter is the most likely form of the CQ-ferriheme complex in aqueous solution.

The preparation of porphyrin S-411 (dehydrocoproporphyrin) and harderoporphyrin from protoporphyrin IX

1981 ◽  
Vol 59 (5) ◽  
pp. 779-785 ◽  
Author(s):  
David Dolphin ◽  
Ramani Sivasothy
Keyword(s):  
Dimethyl Ester ◽  
Protoporphyrin Ix ◽  
The Other ◽  
Side Chain ◽  
Side Chains ◽  
Positional Isomers ◽  
Other Hand ◽  
Hydroxyethyl Group

Protoporphyrin IX dimethyl ester has been converted into the two 2,4-positional isomers bearing hydroxyethyl and methoxycarbonylvinyl side chains. The 4-(2-hydroxyethyl) group was extended to a methoxycarbonylethyl group to give the tetramethyl ester of porphyrin S-411 (2-methoxycarbonylvinyl-4-methoxycarbonylethyldeuteroporphyrin dimethyl ester). On the other hand reduction of the 4-methoxycarbonylvinyl to the corresponding methoxycarbonylethyl group and dehydration of the 2-(2-hydroxyethyl) to a vinyl side chain gave the trimethyl ester of harderoporphyrin (2-vinyl-4-methoxycarbonylethyldeuteroporphyrin dimethyl ester).

A comprehensive in silico study towards understanding the inhibitory mechanism of Lactoperoxidase by Dapsone and Propofol

2020 ◽  
Vol 16 ◽  
Author(s):  
Rameez Jabeer Khan ◽  
Rajat Kumar Jha ◽  
Gizachew Muluneh Amera ◽  
Jayaraman Muthukumaran ◽  
Rashmi Prabha Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Binding Free Energy ◽  
Protoporphyrin Ix ◽  
Md Simulations ◽  
Prosthetic Group ◽  
Drug Molecules ◽  
Group A ◽  
Complex Forms ◽  
Covalently Linked

Introduction: Lactoperoxidase (LPO) is a member of mammalian heme peroxidase family and is an enzyme of innate immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (H2O2) and shows a broad range of antimicrobial activity. Methods: In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which are earlier reported as potent inhibitors of LPO. Whereas the stereochemistry and mode of binding of dapsone and propofol to LPO is still not known because of the lack of the crystal structure of LPO with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation studies of LPO in native and complex forms with dapsone and propofol. Results: From the docking results, the estimated binding free energy (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) was observed for dapsone, and propofol, respectively. The standard error of Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results alone were inconclusive. Conclusion: To further validate the docking results, we performed MD simulation on unbound, and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.

Types A and D Trichothecene Mycotoxins from the Fungus Myrothecium roridum

Planta Medica ◽  
2019 ◽  
Vol 85 (09/10) ◽  
pp. 774-780 ◽  
Author(s):  
Waranya Lakornwong ◽  
Kwanjai Kanokmedhakul ◽  
Kasem Soytong ◽  
Arm Unartngam ◽  
Sarawut Tontapha ◽  
...  
Keyword(s):  
Fungal Biomass ◽  
Macrocyclic Lactone ◽  
Antimalarial Activity ◽  
Pathogenic Fungus ◽  
The Other ◽  
Spectroscopic Methods ◽  
Type D ◽  
Vero Cell Line ◽  
Type A Trichothecenes ◽  
Myrothecium Roridum

AbstractChromatographic separation of extracts from the fungal biomass of a plant pathogenic fungus, Myrothecium roridum, yielded 8 trichothecene toxins including 6 type D trichothecenes (1–6) and 2 type A trichothecenes (7–8). 6′,12′-Epoxymyrotoxin A (1) and 7′-hydroxymytoxin B (2) were new macrocyclic trichothecenes, while the other trichothecenes were identified as myrotoxin B (3), myrotoxin D hydrate (4), 2′,3′-epoxymyrothecine A (5), miotoxin A (6), and 2 trichothecenes lacking the macrocyclic lactone system, roridin L-2 (7) and trichoverritone (8). The structures of these mycotoxins were characterized using spectroscopic methods. The absolute configurations of 1 and 2 were determined by NOESY and a comparison of their experimental and calculated ECD spectra. Most of these mycotoxins (1–4 and 6) exhibited highly potent antimalarial activity against Plasmodium falciparum. They also showed strong cytotoxicity towards KB and NCI-H187 cell lines (IC50 0.60 – 112.28 nM), as well as the Vero cell line (IC50 1.50 – 46.51 nM).

A new three-dimensional anionic cadmium(II) dicyanamide network

2014 ◽  
Vol 70 (11) ◽  
pp. 1054-1056 ◽  
Author(s):  
Qiang Li ◽  
Hui-Ting Wang
Keyword(s):  
Crystal Structure ◽  
Aqueous Solution ◽  
Unit Cell Volume ◽  
Three Dimensional ◽  
Building Blocks ◽  
The Other ◽  
Dimensional Structure ◽  
Cadmium Nitrate ◽  
Nitrate Tetrahydrate ◽  
Anionic Framework

A new cadmium dicyanamide complex, poly[tetramethylphosphonium [μ-chlorido-di-μ-dicyanamido-κ4N1:N5-cadmium(II)]], [(CH3)4P][Cd(NCNCN)2Cl], was synthesized by the reaction of tetramethylphosphonium chloride, cadmium nitrate tetrahydrate and sodium dicyanamide in aqueous solution. In the crystal structure, each CdIIatom is octahedrally coordinated by four terminal N atoms from four anionic dicyanamide (dca) ligands and by two chloride ligands. The dicyanamide ligands play two different roles in the building up of the structure; one role results in the formation of [Cd(dca)Cl]2building blocks, while the other links the building blocks into a three-dimensional structure. The anionic framework exhibits a solvent-accessible void of 673.8 Å3, amounting to 47.44% of the total unit-cell volume. The cavities in the network are occupied by pairs of tetramethylphosphonium cations.

scholarly journals Removal of Chromium from Aqueous Solution Using Modified Pomegranate Peel:Mechanistic and Thermodynamic Studies

2009 ◽  
Vol 6 (s1) ◽  
pp. S153-S158 ◽  
Author(s):  
Tariq S. Najim ◽  
Suhad A. Yassin
Keyword(s):  
Activation Energy ◽  
Solid Solution ◽  
Aqueous Solution ◽  
Adsorption Process ◽  
Batch Process ◽  
The Other ◽  
Water Molecules ◽  
Pomegranate Peel ◽  
Solution Interface ◽  
Adsorbent Surface

Modified pomegranate peel (MPGP) and formaldehyde modified pomegranate peel (FMPGP) were prepared and used as adsorbent for removal of Cr(VI) ions from aqueous solution using batch process. The temperature variation study of adsorption on both adsorbents revealed that the adsorption process is endothermic, from the positive values of ∆H˚. These values lie in the range of physisorption. The negative values of ∆G˚ show the adsorption is favorable and spontaneous. On the other hand, these negative values increases with increase in temperature on both adsorbents, which indicate that the adsorption is preferable at higher temperatures. ∆S˚ values showed that the process is accompanied by increase in disorder and randomness at the solid solution interface due to the reorientation of water molecules and Cr(VI) ions around the adsorbent surface. The endothermic nature of the adsorption was also confirmed from the positive values of activation energy, Ea, the low values of Ea confirm the physisorption mechanism of adsorption. The sticking probability, S*, of Cr(VI) ion on surface of both adsorbents showed that the adsorption is preferable due to low values of S*(0< S*< 1 ), but S*values are lower for FMPGP indicating that the adsorption on FMPGP is more preferable .

Antimalarial activity of the bisquinoline trans-N1,N2-bis (7-chloroquinolin-4-yl)cyclohexane-1,2-diamine: comparison of two stereoisomers and detailed evaluation of the S,S enantiomer, Ro 47-7737.

1997 ◽  
Vol 41 (3) ◽  
pp. 677-686 ◽  
Author(s):  
R G Ridley ◽  
H Matile ◽  
C Jaquet ◽  
A Dorn ◽  
W Hofheinz ◽  
...  
Keyword(s):  
Antimalarial Activity ◽  
Ex Vivo ◽  
The Other ◽  
Parasite Resistance ◽  
Curative Effect ◽  
Specific Process ◽  
Terminal Half Life ◽  
Detailed Evaluation ◽  
Oral Doses

The S,S enantiomer of the bisquinoline trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine, Ro 47-7737, is significantly more potent against chloroquine-resistant Plasmodium falciparum than the R,R enantiomer and the previously described racemate. Both the enantiomers and the racemate are more potent inhibitors of heme polymerization than chloroquine, and their activities are probably mediated by inhibition of this parasite-specific process. The S,S enantiomer, Ro 47-7737, was studied in more detail and proved to be a potent antimalarial in the treatment of P. vivax ex vivo and P. berghei in vivo. Its suppression of P. berghei growth in a mouse model (50% effective dose, 2.3 mg/kg of body weight) was equal to that of chloroquine and mefloquine, and Ro 47-7737 was found to be more potent than these two drugs in the Rane test, in which the curative effect of a single dose is monitored. The dose at which 50% of animals were permanently cured (34 mg/kg) was markedly superior to those of chloroquine (285 mg/kg) and mefloquine (> 250 mg/kg). When administered orally at 50 mg/kg, Ro 47-7737 also showed a faster clearance of parasites than either chloroquine or mefloquine, and unlike the other two compounds, Ro 47-7737 showed no recrudescence. In a study to compare prophylactic efficacies of oral doses of 50 mg/kg, Ro 47-7737 provided protection for 14 days compared to 3 days for mefloquine and 1 day for chloroquine. The good curative and prophylactic properties of the compound can be explained in part by its long terminal half-life. The ability to generate parasite resistance to Ro 47-7737 was also assessed. With a rodent model, resistance could be generated over eight passages. This rate of resistance generation is comparable to that of mefloquine, which has proved to be an effective antimalarial for many years. Toxicity liabilities, however, ruled out this compound as a candidate for drug development.

scholarly journals Succinic acid in aqueous solution: connecting microscopic surface composition and macroscopic surface tension

2014 ◽  
Vol 16 (39) ◽  
pp. 21486-21495 ◽  
Author(s):  
Josephina Werner ◽  
Jan Julin ◽  
Maryam Dalirian ◽  
Nønne L. Prisle ◽  
Gunnar Öhrwall ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Surface Tension ◽  
Succinic Acid ◽  
Photoelectron Spectroscopy ◽  
Surface Composition ◽  
Md Simulations ◽  
Vapor Interface ◽  
X Ray ◽  
Ph Values ◽  
Microscopic Surface

The water–vapor interface of aqueous solutions of succinic acid, where pH values and bulk concentrations were varied, has been studied using surface sensitive X-ray photoelectron spectroscopy (XPS) and molecular dynamics (MD) simulations.

scholarly journals Some Observations on Psychopathy

1966 ◽  
Vol 11 (2) ◽  
pp. 132-139
Author(s):  
Donald J. Mcculloch
Keyword(s):  
Antisocial Behaviour ◽  
Convincing Evidence ◽  
The Other ◽  
Treatment Programs ◽  
Human Being ◽  
The Family ◽  
The One ◽  
Sexual Object ◽  
Socializing Agents ◽  
Identical Behaviour

There is no convincing evidence to support the view that antisocial behaviour can be accounted for by reference to concepts such as learning defect, immaturity or lack of moral fibre. The criminal displays behaviour towards authorities identical to that displayed by a patriot in an occupied country towards the enemy. This identical behaviour, it is asserted by some, shows in the one case instability, cowardice, lack of resolve and in the other case, stability, courage, resolve and strength of will. These statements reveal the attitudes and bias of the observer without illuminating the situation of the observed. It is more relevant to examine what the psychopath has learned and the conditions in which his learning took place than to pursue enquiries aimed at demonstrating a learning defect. The human being is born without the attitudes, beliefs and sentiments towards e.g. property, sexual object etc., which are necessary for his successful incorporation into his ongoing social group. It is the intention of society's socializing agents, the family and the school, to inculcate in the developing human being these necessary attitudes, sentiments and beliefs. Psychopathic personalities are the consequence of the socializing process gone wrong. This paper describes the types of psychopath together with the learning situations which brought them about. The implications for treatment programs are examined.

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