scholarly journals Drug-Membrane Interactions Studied in Phospholipid Monolayers Adsorbed on Nonporous Alkylated Microspheres

2007 ◽  
Vol 12 (2) ◽  
pp. 186-202 ◽  
Author(s):  
Viera Lukacova ◽  
Ming Peng ◽  
Gail Fanucci ◽  
Roman Tandlich ◽  
Anne Hinderliter ◽  
...  
Keyword(s):  
Transition Temperature ◽  
Partition Coefficients ◽  
Temperature Pattern ◽  
Drug Candidates ◽  
Phospholipid Monolayers ◽  
Successful Prediction ◽  
Slow Transport

Characterization of interactions with phospholipids is an integral part of the in vitro profiling of drug candidates because of the roles the interactions play in tissue accumulation and passive diffusion. Currently used test systems may inadequately emulate the bilayer core solvation properties (immobilized artificial membranes [IAM]), suffer from potentially slow transport of some chemicals (liposomes in free or immobilized forms), and require a tedious separation (if used for free liposomes). Here the authors introduce a well-defined system overcoming these drawbacks: nonporous octadecylsilica particles coated with a self-assembled phospholipid monolayer. The coating mimics the structure of the headgroup region, as well as the thickness and properties of the hydrocarbon core, more closely than IAM. The monolayer has a similar transition temperature pattern as the corresponding bilayer. The particles can be separated by filtration or a mild centrifugation. The partitioning equilibria of 81 tested chemicals were dissected into the headgroup and core contributions, the latter using the alkane/water partition coefficients. The deconvolution allowed a successful prediction of the bilayer/water partition coefficients with the standard deviation of 0.26 log units. The plate-friendly assay is suitable for high-throughput profiling of drug candidates without sacrificing the quality of analysis or details of the drug-phospholipid interactions.

scholarly journals Characterization of quality of sediments from Paranaguá Bay (Brazil) by combined in vitro bioassays and chemical analyses

2016 ◽  
Vol 36 (7) ◽  
pp. 1811-1819 ◽  
Author(s):  
Juliane Rizzi ◽  
Elisabet Pérez-Albaladejo ◽  
Denise Fernandes ◽  
Javier Contreras ◽  
Sandro Froehner ◽  
...  
Keyword(s):  
Chemical Analyses ◽  
Paranaguá Bay ◽  
In Vitro Bioassays

scholarly journals In Vitro Resistance against DNA Gyrase Inhibitor SPR719 in Mycobacterium avium and Mycobacterium abscessus

2022 ◽  
Author(s):  
Wassihun Wedajo Aragaw ◽  
Nicole Cotroneo ◽  
Suzanne Stokes ◽  
Michael Pucci ◽  
Ian Critchley ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Dna Gyrase ◽  
Mycobacterium Abscessus ◽  
Drug Candidates ◽  
New Antibiotics ◽  
Novel Drug ◽  
Emergence Of Resistance

Clinical emergence of resistance to new antibiotics affects their utility. Characterization of in vitro resistance is a first step in the profiling of resistance properties of novel drug candidates.

scholarly journals Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Philip J. M. Brouwer ◽  
Aleksandar Antanasijevic ◽  
Zachary Berndsen ◽  
Anila Yasmeen ◽  
Brooke Fiala ◽  
...  
Keyword(s):  
Animal Models ◽  
High Efficiency ◽  
Neutralizing Antibody ◽  
Two Component ◽  
Nanoparticle System ◽  
Hiv 1 ◽  
Component Protein

Abstract The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

scholarly journals Sensitivity of Colletotrichum truncatum to Four Fungicides and Characterization of Thiabendazole-Resistant Isolates

Plant Disease ◽  
2015 ◽  
Vol 99 (11) ◽  
pp. 1590-1595 ◽  
Author(s):  
C. Torres-Calzada ◽  
R. Tapia-Tussell ◽  
I. Higuera-Ciapara ◽  
R. Martin-Mex ◽  
A. Nexticapan-Garcez ◽  
...  
Keyword(s):  
Effective Control ◽  
Common Disease ◽  
Colletotrichum Truncatum ◽  
Physic Nut ◽  
Fungicide Sensitivity ◽  
Tropical Crops ◽  
Control Schemes

Anthracnose, caused by Colletotrichum truncatum (syn. C. capsici), has become a common disease of tropical crops, severely affecting the quantity and quality of fruit and seed and, therefore, reducing their market value. For years, chemical control has been extensively used for managing this disease. However, the appearance of isolates that are resistant to the most commonly employed fungicides is increasingly widespread. Twenty C. truncatum isolates from pepper, papaya, and physic nut were tested in vitro against four fungicides to determine their sensitivity. All evaluated isolates were resistant to azoxystrobin and thiabendazole and susceptible to cyprodinil + fludioxonil and mancozeb. To determine the molecular mechanism conferring thiabendazole resistance, the TUB-2 gene was characterized, revealing a glutamic acid to alanine substitution at position 198 in 6 of the 20 isolates that were tested. This work confirms the emergence of benzimidazole-based fungicide resistance in C. truncatum populations and highlights the need for monitoring fungicide sensitivity as an essential activity for the development of effective control schemes.

scholarly journals Rapid Rubber Extraction and NMR Spectroscopy of Rubber, Extracted from the Endemic Species Scorzonera Tau-Saghyz

2020 ◽  
Vol 22 (1) ◽  
pp. 59
Author(s):  
K.K. Boguspaev ◽  
S.K. Turasheva ◽  
T.M. Seilkhanov ◽  
D.G. Faleev ◽  
M.S. Mutalkhanov ◽  
...  
Keyword(s):  
Adventitious Shoots ◽  
Physiological Age ◽  
Root Extract ◽  
Nmr Characterization ◽  
First Time ◽  
Rubber Good ◽  
Isoprene Rubber

Scorzonera tau-saghyz Lipsch. et G.G. Bosse is an endemic rubber producing plant, growing in mountain regions in South Kazakhstan. The rubber content in plants and the quality of biopolymer has an important impact on industrial rubber production. The results of this study showed that the amount of rubber in S. tau-saghyz roots fluctuates between 7.74% and 38.75%. The amount of synthesized and deposited rubber biopolymer particles depends on various factors such as physiological age of plant, origin, temperature, moisture and environmental conditions. We optimized the extraction method of natural rubber by using n-hexane as a solvent for direct extraction. This method allows extracting the maximum amount of rubber from 3‒4-year-old plants. NMR results show structural links of natural isoprene rubber in the root extract sample. There is a clear relationship between methyl, methine and methylene protons which corresponds to isoprene rubber structure. The samples having strongly marked singlets that are inherent for rubber functional groups confirms the stereospecific structure of rubber. Good solubility of the root extract in deuterated chloroform can characterize the low molecular weight of the polymer. NMR characterization of rubber, extracted from S. tau-saghyz roots, is reported for the first time. Regeneration in vitro provides an important opportunity for endemic preservation by rapidly increasing the number of plants. The best regeneration of adventitious shoots was obtained on MS medium containing 5.5 μM kinetin and 0.5 μM NAA. The plants were successfully acclimatized in a glasshouse with 75% of S. tau-saghyz plantlets, respectively surviving after transfer to ex vitro conditions.

scholarly journals FORMULATION DEVELOPMENT AND CHARACTERIZATION OF TRIAMCINOLONE LOADED CUBOSOMES FOR TRANSDERMAL DRUG DELIVERY

2021 ◽  
Vol 6 (12) ◽  
pp. 1-17
Author(s):  
C. Pandian ◽  
A.Abdul Hasan Sathali ◽  
G. Abirami ◽  
E. Krithika
Keyword(s):  
Transdermal Delivery ◽  
In Vitro Release ◽  
Poloxamer 407 ◽  
Formulation Development ◽  
Inflammatory Reactions ◽  
Barrier Effects ◽  
Low Solubility

Psoriasis is a chronic condition that is caused by the negative signals given by immune system, which leads to hyperproliferation and other inflammatory reactions on the skin. These conditions may adversely affect the quality of the patient’s life leading to psychological stress. Topical delivery of drug is always preferred for Psoriasis because other treatments may lead to systemic intoxication and other adverse reactions. Triamcinolone is a topical corticosteroid belonging to BCS class IV (low solubility and permeability) used to treat Psoriasis. The limitations with transdermal delivery is that only a small amount of the drug can be transferred through the skin tissue due to the barrier effects of the Stratum corneum. Therefore, Novel transdermal delivery system, Cubosomes belonging to Nanostructured lipid carriers were chosen to overcome the issues of solubility and permeability. Twelve formulations were prepared with various ratios of Glyceryl monooleate (2.5 to 5%) & Poloxamer 407 (0.5 to 2%) and the formulations were evaluated for particle size, PDI, zeta potential, entrapment efficacy, drug content and in-vitro release. The best composition of Cubosomes was selected and incorporated into transdermal patch and the formulated patches were evaluated.

scholarly journals Cheminformatic Characterization of Natural Antimicrobial Products for the Development of New Lead Compounds

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3970
Author(s):  
Samson Olaitan Oselusi ◽  
Alan Christoffels ◽  
Samuel Ayodele Egieyeh
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Potential Drug ◽  
Natural Antimicrobial ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Multidrug Resistant Pathogens

The growing antimicrobial resistance (AMR) of pathogenic organisms to currently prescribed drugs has resulted in the failure to treat various infections caused by these superbugs. Therefore, to keep pace with the increasing drug resistance, there is a pressing need for novel antimicrobial agents, especially from non-conventional sources. Several natural products (NPs) have been shown to display promising in vitro activities against multidrug-resistant pathogens. Still, only a few of these compounds have been studied as prospective drug candidates. This may be due to the expensive and time-consuming process of conducting important studies on these compounds. The present review focuses on applying cheminformatics strategies to characterize, prioritize, and optimize NPs to develop new lead compounds against antimicrobial resistance pathogens. Moreover, case studies where these strategies have been used to identify potential drug candidates, including a few selected open-access tools commonly used for these studies, are briefly outlined.

scholarly journals PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariam Lofty Khaled ◽  
Yelena Bykhovskaya ◽  
Chunfang Gu ◽  
Alice Liu ◽  
Michelle D. Drewry ◽  
...  
Keyword(s):  
Gene Trap ◽  
Whole Exome ◽  
The Us ◽  
Related Quality ◽  
First Time

AbstractKeratoconus (KC) is the most common corneal ectatic disorder affecting >300,000 people in the US. KC normally has its onset in adolescence, progressively worsening through the third to fourth decades of life. KC patients report significant impaired vision-related quality of life. Genetic factors play an important role in KC pathogenesis. To identify novel genes in familial KC patients, we performed whole exome and genome sequencing in a four-generation family. We identified potential variants in the PPIP5K2 and PCSK1 genes. Using in vitro cellular model and in vivo gene-trap mouse model, we found critical evidence to support the role of PPIP5K2 in normal corneal function and KC pathogenesis. The gene-trap mouse showed irregular corneal surfaces and pathological corneal thinning resembling KC. For the first time, we have integrated corneal tomography and pachymetry mapping into characterization of mouse corneal phenotypes which could be widely implemented in basic and translational research for KC diagnosis and therapy in the future.

scholarly journals Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2696 ◽  
Author(s):  
Teran ◽  
Guevara ◽  
Mora ◽  
Dobronski ◽  
Barreiro-Costa ◽  
...  
Keyword(s):  
Schiff Base ◽  
Schiff Bases ◽  
Antimicrobial Activities ◽  
Drug Candidates ◽  
Development Of Resistance ◽  
Schiff Base Derivatives ◽  
Wide Range ◽  
Derivatives Of

Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.

Sign in / Sign up

Export Citation Format

Share Document