Bioconversion of substrate of low solubility in water by bacterial cells immobilized on the surface of unwoven cloth coated with a pyridinium-type polymer

Introduction. Aspects of the use of nitrofurans for external use (nitrofural, furazolidone and furazidin) are described in the article. Review of current research that is dedicated to development of drugs containing nitrofuran derivatives has been carried out. The prospects for creating dosage forms of furaсillin and furazolidone containing their solid dispersions with polymers are considered.Text. The group of nitrofurans is widely in demand in the modern pharmaceutical market. The most common active ingredients – furacillin, furazolidone and furazidin are represented by various dosage forms for both internal and external use. All nitrofuran derivatives have a wide spectrum of antimicrobial action and a specific mechanism of action on bacterial cells. The low level of development of antimicrobial resistance allows nitrofurans to remain one of the most effective chemotherapeutic groups of antimicrobial compounds for many decades. The review shows a numerous current developments carried out by both Russian and foreign authors about use of furacillin, furadonin and furazidin to develop the composition of new drugs, including combination drugs, as well as promising treatment methods. Currently, on the basis of Sechenov University, research is actively conducted to increase the solubility and dissolution rate of nitrofurans in water using the method of solid dispersions. Also, work is underway to develop the composition and technology of solid (instant) dosage forms granules and tablets, and soft dosage forms gels containing furacillin and furazolidone as active substances.Conclusion. Despite the use of active substances from the nitrofuran group in pharmaceutical practice for more than half a century and their low solubility in water, research on the development of complex drugs for external use and mono-preparations of nitrofurans have not lost their relevance and are actively conducted to this day.

Download Full-text

Evaluation of pharmacokinetic properties of isobornylphenols in silico

The Siberian Journal of Clinical and Experimental Medicine ◽

10.29001/2073-8552-2020-35-4-79-86 ◽

2020 ◽

Vol 35 (4) ◽

pp. 79-86

Author(s):

O. I. Ostrikova ◽

O. E. Vaizova ◽

O. I. Aliev ◽

E. V. Buravlev ◽

I. Yu. Chukicheva ◽

...

Keyword(s):

Toxicity Assessment ◽

Pharmacokinetic Parameters ◽

Structure Property ◽

Solubility In Water ◽

Virtual Tools ◽

Internet Resources ◽

P Glycoprotein ◽

Pharmacokinetic Properties ◽

Low Toxicity ◽

Low Solubility

Introduction. The potential of a new compound in the ongoing drugs discovery process is initially explored using virtual instruments, where its activity is predicted based on its molecular structure.Aim. This study aimed to evaluate the pharmacokinetic parameters and possible toxicity of isobornyl compounds based on virtual tools.Material and Methods. Several free Internet resources were used to assess the absorption, distribution, metabolism, excretion (ADME), and toxicity (T) of 2,6-diisobornyl-4-methylphenol (1, Dibornol), 2-hydroxy-3-isobornyl-5-methylbenzaldehyde (2), and 2-((di-n-butylamino) methyl)-6-isobornyl-4-methylphenol (3). Pharmacokinetic properties were calculated on ADMETlab platform. Toxicity and physical properties were evaluated using TEST software based on the structure-property quantification models of organic substances according to structure–property principle. Web server ProTox_II was used for acute toxicity assessment.Results. Plasma protein binding degrees were 76,9% for (1), 85,9% for (2), and 91,8% for (3). All three compounds were capable of penetrating the blood-brain barrier. Dibornol was identified neither as a substrate nor as an inhibitor of P-glycoprotein unlike (2) and (3). The half-life of all compounds was short (about 2 hours); the clearance was slow (about 2 mL/min*kg). The study showed that (2) and (3) potentially exert the toxic effects during the developmental stage of the organism, while ADMETlab showed potential cardio- and hepatotoxicity for (2) and (3), respectively. All compounds had extremely low solubility in water, which affected the assessments of other indicators by TEST software. The ProTox_II server showed the extremely low toxicity LD50 for all compounds (toxicity class 5).

Download Full-text

New Active Pharmaceutical Ingredient-Ionic Liquids (API-ILs) Derived from Indomethacin and Mebendazole

Proceedings ◽

10.3390/ecsoc-22-05781 ◽

2018 ◽

Vol 9 (1) ◽

pp. 48 ◽

Cited By ~ 7

Author(s):

◽

Emilia Tojo

Keyword(s):

Ionic Liquids ◽

Water Solubility ◽

Methanesulfonic Acid ◽

Active Pharmaceutical Ingredient ◽

High Water ◽

Solubility In Water ◽

Pharmaceutical Ingredients ◽

Low Toxicity ◽

Low Solubility ◽

High Water Solubility

The transformation of two solid Active Pharmaceutical Ingredients (APIs) into new ionic liquids (IL)s that incorporate APIs (API-ILs) is reported. The structures of the APIs (indomethacin and mebendazole) were selected by their susceptibility to being transformed into API-ILs (either to form the cation or the anion) and their limited bioavailability due to their low solubility in water. The counterions, such as those derived from 2-dimethylaminoethanol (DMEA), tetramethylguanidine (TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2] (TED), p-toluensulfonic acid, glycolic acid, methanesulfonic acid, and saccharin, were carefully chosen, aiming for high biocompatibility, low toxicity, and high water solubility. The synthesis was carried out by direct treatment of the API with the corresponding selected acid or base. Finally, the solubility in water of all the synthesized salts was determined.

Download Full-text

Ruthenacarborane–Phenanthroline Derivatives as Potential Metallodrugs

Molecules ◽

10.3390/molecules25102322 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2322

Author(s):

Martin Kellert ◽

Imola Sárosi ◽

Rajathees Rajaratnam ◽

Eric Meggers ◽

Peter Lönnecke ◽

...

Keyword(s):

Single Crystal ◽

Diffraction Analysis ◽

Organic Solvents ◽

Side Product ◽

Ambient Conditions ◽

Carbonyl Ligand ◽

Single Crystal Diffraction ◽

Solubility In Water ◽

Low Solubility

Ruthenium-based complexes have received much interest as potential metallodrugs. In this work, four RuII complexes bearing a dicarbollide moiety, a carbonyl ligand, and a phenanthroline-based ligand were synthesized and characterized, including single crystal diffraction analysis of compounds 2, 4, and 5 and an observed side product SP1. Complexes 2–5 are air and moisture stable under ambient conditions. They show excellent solubility in organic solvents, but low solubility in water.

Download Full-text

Uptake and Excretion of Chemicals by Aquatic Fauna

Water Science & Technology ◽

10.2166/wst.1983.0190 ◽

1983 ◽

Vol 15 (S1) ◽

pp. 67-78

Author(s):

V Zitko

Keyword(s):

Molecular Weight ◽

Flame Retardants ◽

Physiological State ◽

Compartment Model ◽

Solubility In Water ◽

Aquatic Fauna ◽

Chlorinated Paraffins ◽

A Minor ◽

Low Solubility

Factors influencing the movement of chemicals across biological membranes are: solubility in lipids and in water, chemical stability, ionization, and molecular weight of the chemical. On the part of aquatic fauna, the transport of chemicals is affected by metabolic activity and by the physiological state of the animals. Additional factors include water temperature, hardness or salinity, and presence of other chemicals. The effects of these factors will be discussed and illustrated by examples. The uptake of highly lipid-soluble compounds by fish appears to be determined by their solubility in water, and compounds with extremely low solubility in water are not taken up in spite of their high solubility in lipids. Examples are hexabromo-benzene, highly brominated biphenyls, C24 chlorinated paraffins, and some flame retardants of the Dechlorane series. In addition to solubility in water, there may be a high molecular weight threshold, beyond which compounds are not taken up, and factors based on the chemical structure of the compounds may play a role as well. For example, Dechlorane 604, a tetrabromophenyl norbornene, is accumulated by fish to a much lesser degree than a tribromophenyl norbornene, present as a minor impurity in Dechlorane 604. Chemical and biochemical stability of compounds are additional factors determining the extent of environmental contamination. Examples are the widespread contamination of aquatic biota by two nonachlors, present originally as relatively minor components in technical chlordane, and the contamination by some components of toxaphene. The use of a one compartment model in studies of accumulation and excretion of chemicals by aquatic fauna, and its extension to the determination of lethality curves, will be mentioned.

Download Full-text

Arrangement of Rh3+ions infac-triamminetrichloridorhodium from powder data and infac-triamminetrinitratorhodium crystals twinned by merohedry

Acta Crystallographica Section C Crystal Structure Communications ◽

10.1107/s010827011303076x ◽

2013 ◽

Vol 69 (12) ◽

pp. 1462-1466 ◽

Cited By ~ 1

Author(s):

Alexander D. Vasiliev ◽

Maxim S. Molokeev ◽

Iraida A. Baidina ◽

Anatoly V. Belyaev ◽

Sofiya N. Vorob'eva

Keyword(s):

Hydrogen Bonds ◽

Single Crystal ◽

Powder Diffraction ◽

Diffraction Data ◽

Rhodium Complexes ◽

Powder Diffraction Data ◽

Threefold Axis ◽

Solubility In Water ◽

Using Data ◽

Low Solubility

The rhodium complexes [RhCl3(NH3)3], (I), and [Rh(NO3)3(NH3)3], (II), are built from octahedral RhX3(NH3)3units; in (I) they are isolated units, while in (II) the units are stacked in columns with partially filled sites for the Rh atoms. The octahedra of monoclinic crystals of (I) are linked by N—H...Cl hydrogen bonds and the Rh3+ions are located on the mirror planes. In the trigonal crystals of (II), the discontinuous `columns' along the threefold axis are linked by N—H...O hydrogen bonds. The structure of (I) has been solved using laboratory powder diffraction data, the structure of (II) has been solved by single-crystal methods using data from a merohedrally twinned sample. Both compounds possess low solubility in water.

Download Full-text

Release of selected amino acids from zinc carriers

Acta Pharmaceutica ◽

10.1515/acph-2016-0024 ◽

2016 ◽

Vol 66 (2) ◽

pp. 269-277

Author(s):

Renata Dyja ◽

Barbara Dolińska ◽

Florian Ryszka

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Molar Ratio ◽

Time Intervals ◽

Solubility In Water ◽

First Order ◽

First Order Kinetics ◽

Acid Release ◽

Co Precipitation ◽

Low Solubility

Abstract The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 μmol of histidine or 17.4 μmol of tryptophan) that provides release of similar amounts of amino acid (4.1–4.6 μmol of histidine or 8.7–9.9 μmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9–11.2 μmol) is limited by the tyrosine low solubility in water.

Download Full-text

Modified Cyclodextrins Solubilize Elemental Sulfur in Water and Enable Biological Sulfane Sulfur Delivery

10.26434/chemrxiv.12525581.v1 ◽

2020 ◽

Author(s):

Sarah Bolton ◽

Michael Pluth

Keyword(s):

Elemental Sulfur ◽

Complex Environments ◽

Solubility In Water ◽

Sulfane Sulfur ◽

New Strategy ◽

Raw 264.7 Macrophage Cells ◽

And Storage ◽

Low Solubility ◽

Important Form ◽

Mediated Reduction

An important form of biological sulfur is sulfane sulfur, or S0, which is found in polysulfide and persulfide compounds as well as in elemental sulfur. Sulfane sulfur, often in the form of S8, functions as a key energy source in the metabolic processes of thermophilic Archaean organisms found in sulfur-rich environments and can be metabolized both aerobically and anaerobically by different archaeons. Despite this importance, S8 has a low solubility in water (~19 nM), raising questions of how it can be solubilized and made chemically accessible in complex environments. Motivated by prior crystallographic data showing S8 binding to hydrophobic motifs in filamentous glycoproteins from the sulfur reducing Staphylothermus marinus anaerobe, we demonstrate that simple hydrophobic motifs, such as 2-hydroxypropyl β-cyclodextrin (2HPβ), are sufficient solubilize S8 at concentrations up to 2.0 ± 0.2 mM in aqueous solution. We demonstrate that the solubilized S8 is chemically accessible, can be reduced with tris(2-carboxyethyl)phosphine (TCEP), and reacts with thiols to generate H2S. The thiol-mediated conversion of 2HPβ/S8 to H2S ranges from 80% to quantitative efficiency for Cys and glutathione (GSH). Moreover, we demonstrate that 2HPβ can catalyze the reaction of Cys-mediated reduction of S8 to H2S in water. Adding to the biological relevance of the developed systems, we demonstrate that treatment of Raw 264.7 macrophage cells with the 2HPβ/S8 complex prior to LPS stimulation reduces NO2– levels, which is consistent with known activities of bioavailable H2S and sulfane sulfur. Taken together, these investigations provide a new strategy for delivering H2S and sulfane sulfur in complex systems and more importantly provide new insights into the chemical accessibility and storage of S0 and S8 in biological environments.

Download Full-text

Modified Cyclodextrins Solubilize Elemental Sulfur in Water and Enable Biological Sulfane Sulfur Delivery

10.26434/chemrxiv.12525581 ◽

2020 ◽

Author(s):

Sarah Bolton ◽

Michael Pluth

Keyword(s):

Elemental Sulfur ◽

Complex Environments ◽

Solubility In Water ◽

Sulfane Sulfur ◽

New Strategy ◽

Raw 264.7 Macrophage Cells ◽

And Storage ◽

Low Solubility ◽

Important Form ◽

Mediated Reduction

An important form of biological sulfur is sulfane sulfur, or S0, which is found in polysulfide and persulfide compounds as well as in elemental sulfur. Sulfane sulfur, often in the form of S8, functions as a key energy source in the metabolic processes of thermophilic Archaean organisms found in sulfur-rich environments and can be metabolized both aerobically and anaerobically by different archaeons. Despite this importance, S8 has a low solubility in water (~19 nM), raising questions of how it can be solubilized and made chemically accessible in complex environments. Motivated by prior crystallographic data showing S8 binding to hydrophobic motifs in filamentous glycoproteins from the sulfur reducing Staphylothermus marinus anaerobe, we demonstrate that simple hydrophobic motifs, such as 2-hydroxypropyl β-cyclodextrin (2HPβ), are sufficient solubilize S8 at concentrations up to 2.0 ± 0.2 mM in aqueous solution. We demonstrate that the solubilized S8 is chemically accessible, can be reduced with tris(2-carboxyethyl)phosphine (TCEP), and reacts with thiols to generate H2S. The thiol-mediated conversion of 2HPβ/S8 to H2S ranges from 80% to quantitative efficiency for Cys and glutathione (GSH). Moreover, we demonstrate that 2HPβ can catalyze the reaction of Cys-mediated reduction of S8 to H2S in water. Adding to the biological relevance of the developed systems, we demonstrate that treatment of Raw 264.7 macrophage cells with the 2HPβ/S8 complex prior to LPS stimulation reduces NO2– levels, which is consistent with known activities of bioavailable H2S and sulfane sulfur. Taken together, these investigations provide a new strategy for delivering H2S and sulfane sulfur in complex systems and more importantly provide new insights into the chemical accessibility and storage of S0 and S8 in biological environments.

Download Full-text

Solubility enhancement of BCS classified IV drug - Apixaban by preparation and evaluation of Mesoporous Nanomatrix

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1910 ◽

2020 ◽

Vol 11 (1) ◽

pp. 880-890

Author(s):

Asati Amit V ◽

Salunkhe Kishor S ◽

Chavan Machindra J ◽

Chintamani Ravindra B ◽

Rajput Singh Rudra Pratap

Keyword(s):

Tin Oxide ◽

Amorphous Solid ◽

Solubility Enhancement ◽

Amorphous Solid Dispersion ◽

Solubility In Water ◽

Efficient Delivery ◽

Effective Delivery ◽

Low Solubility ◽

Class Iv

Biopharmaceutics classification system (BCS) class IV compounds, exhibits low solubility, intestinal permeability and oral bioavailability among all the pharmaceutical class of drugs. Therefore, these drugs need a more compatible and efficient delivery system. Since, their solubility in various mediums will remains a limitation. Hence, the mesoporous Nanomatrix approach may prove to be a suitable solution ahead. Therefore, in the present study, the polymer-coated mesoporous material like Sylysia 350, Carbon, Tin Oxide are opted for the BCS class IV drug like Apixaban to attain higher solubility and dissolution. The prepared Nanomatrix was evaluated for its particle size, DSC, Solubility and dissolution studies. For this study, Apixaban was opted for formulating Sylysia 350, Carbon, Tin Oxide based Mesoporous Nanomatrix system. Nanomatrix was prepared by the Amorphous solid dispersion method using probe sonication. The mesoporous Nanomatrix of Apixaban showed improvement in the solubility in water by approx.7 folds when Apixaban used in combination with Sylysia 350 and Polymer HPMC K15M. From the present study, we can conclude that the optimized Apixaban mesoporous Nanomatrix may prove to be a suitable potential option for solubility enhancement, increase in-vitro drug release and effective delivery of BCS class IV drugs.

Download Full-text