scholarly journals Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity

2021 ◽  
Vol 22 (23) ◽  
pp. 12675
Author(s):  
Michal Rouchal ◽  
Jana Rudolfová ◽  
Vladimír Kryštof ◽  
Veronika Vojáčková ◽  
Richard Čmelík ◽  
...  
Keyword(s):  
Biological Activity ◽  
Chemical Properties ◽  
Docking Study ◽  
Binding Pocket ◽  
Drug Binding ◽  
Solubility In Water ◽  
Cyclin Dependent Kinases ◽  
Adamantane Skeleton ◽  
The Cost ◽  
Low Solubility

Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug’s solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.

Chitosan and Its Derivatives - Biomaterials with Diverse Biological Activity for Manifold Applications

2019 ◽  
Vol 19 (9) ◽  
pp. 737-750 ◽  
Author(s):  
Paulina Paul ◽  
Beata Kolesinska ◽  
Witold Sujka
Keyword(s):  
Biological Activity ◽  
Biomedical Applications ◽  
Chemical Properties ◽  
Alkaline Solutions ◽  
Chemical Modifications ◽  
Solubility In Water ◽  
Chitosan Derivatives ◽  
Main Obstacle ◽  
Derivatives Of ◽  
Diverse Biological Activity

Derived from chitin, chitosan is a natural polycationic linear polysaccharide being the second most abundant polymer next to cellulose. The main obstacle in the wide use of chitosan is its almost complete lack of solubility in water and alkaline solutions. To break this obstacle, the structure of chitosan is subjected to modification, improving its physic-chemical properties and facilitating application as components of composites or hydrogels. Derivatives of chitosan are biomaterials useful for different purposes because of their lack of toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the methods of chemical modifications of chitosan which allow to obtain tailor- made properties required for a variety of biomedical applications. Selected pharmaceutical and biomedical applications of chitosan derivatives are also highlighted. Possibility to manage waste from arthropod and crab processing is also emphasized.

Synthesis and characterization of a reconstituted myoglobin-chlorin e6 adduct for theranostic applications

2020 ◽  
Vol 24 (05n07) ◽  
pp. 887-893
Author(s):  
Matteo Di Giosia ◽  
Damiano Genovese ◽  
Andrea Cantelli ◽  
Matteo Cingolani ◽  
Enrico Rampazzo ◽  
...  
Keyword(s):  
Photophysical Properties ◽  
Emission Spectra ◽  
Fold Increase ◽  
Binding Pocket ◽  
Chlorin E6 ◽  
High Tendency ◽  
Solubility In Water ◽  
Theranostic Applications ◽  
Low Solubility

Chlorin e6 (Ce6) and its derivatives are among the most important photosensitizers in photodynamic therapy. Due to their intense fluorescence, chlorins may also be used for diagnostics. However, low solubility in water and high tendency to aggregation restrict their medical use. Here we demonstrate that apo-myoglobin, by reinserting Ce6 in its heme binding pocket, can be used to monomolecularly disperse it. The reconstructed myoglobin-Ce6 adduct presents noticeable changes in the photophysical properties of the chromophore. A red-shift, in particular in the transparency window, can be observed in the absorption and in the emission spectra of the adduct compared to the spectra of the free chlorin in PBS. The adduct presents a higher quantum yield and an increased excited-state lifetime with respect to the free Ce6. The binding of Ce6 to apo-myoglobin determines a decrease of the 1O2 generation but a three-fold increase of peroxides production, determining globally an increase in the performance of Ce6 as a photosensitizer and imaging agent.

Theoretical Exploration of 2,2’-Bipyridines as Electro-Active Compounds in Flow Batteries

2019 ◽  
Author(s):  
Mariano Sánchez-Castellanos ◽  
Martha M. Flores-Leonar ◽  
Zaahel Mata-Pinzón ◽  
Humberto G. Laguna ◽  
Karl García-Ruiz ◽  
...  
Keyword(s):  
Redox Potential ◽  
Active Material ◽  
Chemical Properties ◽  
Small Subset ◽  
Solubility In Water ◽  
Protonation Reaction ◽  
Redox Active ◽  
Physico Chemical ◽  
Pka Value ◽  
Flow Batteries

Compounds from the 2,2’-bipyridine molecular family were investigated for use as redox-active materials in organic flow batteries. For 156 2,2’-bipyridine derivatives reported in the academic literature, we calculated the redox potential, the pKa for the first protonation reaction, and the solubility in aqueous solutions. Using experimental data on a small subset of derivatives, we were able to calibrate our calculations. We find that functionalization with electron-withdrawing groups leads to an increase of the redox potential and to an increase of the molecular acidity (as expressed in a reduction of the pKa value for the first protonation step). Furthermore, calculations of solubility in water indicate that some of the studied derivatives have adequate solubility for flow battery applications. Based on an analysis of the physico-chemical properties of the 156 studied compounds, we down-select five molecules with carbonyl- and nitro-based functional groups, whose parameters are especially promising for potential application as negative redox-active material inorganic flow batteries.

Theoretical Exploration of 2,2’-Bipyridines as Electro-Active Compounds in Flow Batteries

2019 ◽  
Author(s):  
Mariano Sánchez-Castellanos ◽  
Martha M. Flores-Leonar ◽  
Zaahel Mata-Pinzón ◽  
Humberto G. Laguna ◽  
Karl García-Ruiz ◽  
...  
Keyword(s):  
Redox Potential ◽  
Active Material ◽  
Chemical Properties ◽  
Small Subset ◽  
Solubility In Water ◽  
Protonation Reaction ◽  
Redox Active ◽  
Physico Chemical ◽  
Pka Value ◽  
Flow Batteries

Compounds from the 2,2’-bipyridine molecular family were investigated for use as redox-active materials in organic flow batteries. For 156 2,2’-bipyridine derivatives reported in the academic literature, we calculated the redox potential, the pKa for the first protonation reaction, and the solubility in aqueous solutions. Using experimental data on a small subset of derivatives, we were able to calibrate our calculations. We find that functionalization with electron-withdrawing groups leads to an increase of the redox potential and to an increase of the molecular acidity (as expressed in a reduction of the pKa value for the first protonation step). Furthermore, calculations of solubility in water indicate that some of the studied derivatives have adequate solubility for flow battery applications. Based on an analysis of the physico-chemical properties of the 156 studied compounds, we down-select five molecules with carbonyl- and nitro-based functional groups, whose parameters are especially promising for potential application as negative redox-active material inorganic flow batteries.

scholarly journals New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2288
Author(s):  
Ahmed Gaber ◽  
Moamen S. Refat ◽  
Arafa A.M. Belal ◽  
Ibrahim M. El-Deen ◽  
Nader Hassan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Analytical Data ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Tetrahedral Geometry ◽  
Thiosemicarbazone Complexes

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.

scholarly journals Silver Nanoparticles Stabilized with Phosphorus-Containing Heterocyclic Surfactants: Synthesis, Physico-Chemical Properties, and Biological Activity Determination

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1883
Author(s):  
Martin Pisárčik ◽  
Miloš Lukáč ◽  
Josef Jampílek ◽  
František Bilka ◽  
Andrea Bilková ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Biological Activity ◽  
Zeta Potential ◽  
Chain Length ◽  
Alkyl Chain ◽  
Chemical Properties ◽  
Alkyl Chain Length ◽  
Microbial Pathogens ◽  
Physico Chemical ◽  
Phosphorus Containing

Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50–60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.

scholarly journals A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica Knox ◽  
Nicolas Joly ◽  
Edmond M. Linossi ◽  
José A. Carmona-Negrón ◽  
Natalia Jura ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Developmental Delay ◽  
Small Molecule ◽  
Parasitic Nematode ◽  
Kinase Inhibitor ◽  
Binding Pocket ◽  
Drug Binding ◽  
Nematode Infection ◽  
Selective Inhibitors ◽  
C Elegans

AbstractOver one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-selective manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematode Caenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant in C. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-selective inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.

scholarly journals Pumilacidin, a complex of new antiviral antibiotics. Production, isolation, chemical properties, structure and biological activity.

1990 ◽  
Vol 43 (3) ◽  
pp. 267-280 ◽  
Author(s):  
NOBUAKI NARUSE ◽  
OSAMU TENMYO ◽  
SEIKICHI KOBARU ◽  
HIDEO KAMEI ◽  
TAKEO MIYAKI ◽  
...  
Keyword(s):  
Biological Activity ◽  
Chemical Properties

Recent Innovations of Organo-Fluorine synthesis and pharmacokinetics

2021 ◽  
Vol 25 ◽  
Author(s):  
Omkar Kamble ◽  
Ramababu Dandela ◽  
Sandip Shinde
Keyword(s):  
Biological Activity ◽  
Pharmacokinetic Study ◽  
Fluorine Atom ◽  
Neurological Diseases ◽  
Research Work ◽  
Chemical Properties ◽  
Physical Property ◽  
Bioactive Molecules ◽  
Pharmacokinetic Property ◽  
Research Areas

: The fluorinated compounds have significance in medicinal chemistry and pharmaceuticals research. The introduction of fluorine atom in the heterocyclic compounds increases biological activity, develops favourable physiochemical interaction. Combination of the heterocycles and fluorine substituent having large scope in the research work of the different drugs molecules. The compounds not only show biological activity but also show unique physical and chemical properties that open the doors of multidisciplinary research areas. Fluorine atom tolerance towards maximum functional groups, simplicity in operation, replacing hydrogen with fluorine of bioactive molecules are more efficient for the production at the commercial level. The fluorine substitution also increases the binding affinity to the targeted protein. Also, incorporation of fluorine into the drug helps to increase the polarity hence to increase the rate of drug metabolism and improves the metabolic stability. The pharmacokinetic study plays an important role in clinical research, since 1996, researcher Whitford discover that the pharmacokinetic of fluorine is depend on its pH and amount in the bone. pH of organofluoride governs the absorption, distribution and excretion of fluoride. It also increases the stability when binding with carbon atom and resulting in an increase in bioactivity. This is the main reason that around 25% of present active drugs on various diseases, including cancer, diabetes, HIV, etc. have fluorine as important content. Not only pharmacokinetic property but also the physical property of the drug can be enhanced or altered by selective insertion at the key place of the fluorine atom in the drug compound. In this report, we have summarized the interesting research article reported since 2000 for the synthesis of low fluorine substituted organic compounds for medicinal research and pharmacokinetic study of fluorine molecules in neurological diseases, cancer, and tuberculosis research.

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