scholarly journals Deciphering Structural Determinants in Chondroitin Sulfate Binding to FGF-2: Paving the Way to Enhanced Predictability of Their Biological Functions

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 313
Author(s):  
Giulia Vessella ◽  
José Antonio Vázquez ◽  
Jesús Valcárcel ◽  
Laura Lagartera ◽  
Dianélis T. Monterrey ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Biological Activities ◽  
3D Structure ◽  
Tight Binding ◽  
Holistic Approach ◽  
Biological Functions ◽  
Comprehensive Understanding ◽  
Structural Determinants ◽  
Chondroitin Sulfates ◽  
Structure Activity

Controlling chondroitin sulfates (CSs) biological functions to exploit their interesting potential biomedical applications requires a comprehensive understanding of how the specific sulfate distribution along the polysaccharide backbone can impact in their biological activities, a still challenging issue. To this aim, herein, we have applied an “holistic approach” recently developed by us to look globally how a specific sulfate distribution within CS disaccharide epitopes can direct the binding of these polysaccharides to growth factors. To do this, we have analyzed several polysaccharides of marine origin and semi-synthetic polysaccharides, the latter to isolate the structure-activity relationships of their rare, and even unnatural, sulfated disaccharide epitopes. SPR studies revealed that all the tested polysaccharides bind to FGF-2 (with exception of CS-8, CS-12 and CS-13) according to a model in which the CSs first form a weak complex with the protein, which is followed by maturation to tight binding with kD ranging affinities from ~1.31 μM to 130 μM for the first step and from ~3.88 μM to 1.8 nM for the second one. These binding capacities are, interestingly, related with the surface charge of the 3D-structure that is modulated by the particular sulfate distribution within the disaccharide repeating-units.

scholarly journals Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides

2021 ◽  
Vol 11 (12) ◽  
pp. 5702
Author(s):  
Ali Irfan ◽  
Sajjad Ahmad ◽  
Saddam Hussain ◽  
Fozia Batool ◽  
Haseeba Riaz ◽  
...  
Keyword(s):  
Literature Review ◽  
Biomedical Applications ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Pharmacological Activities ◽  
Lead Compounds ◽  
Structure Activity ◽  
Wide Range ◽  
Sulfonamide Group

Quinoxaline is a privileged pharmacophore that has broad-spectrum applications in the fields of medicine, pharmacology and pharmaceutics. Similarly, the sulfonamide moiety is of considerable interest in medicinal chemistry, as it exhibits a wide range of pharmacological activities. Therefore, the therapeutic potential and biomedical applications of quinoxalines have been enhanced by incorporation of the sulfonamide group into their chemical framework. The present review surveyed the literature on the preparation, biological activities and structure-activity relationship (SAR) of quinoxaline sulfonamide derivatives due to their broad range of biomedical activities, such as diuretic, antibacterial, antifungal, neuropharmacological, antileishmanial, anti-inflammatory, anti-tumor and anticancer action. The current biological diagnostic findings in this literature review suggest that quinoxaline-linked sulfonamide hybrids are capable of being established as lead compounds; modifications on quinoxaline sulfonamide derivatives may give rise to advanced therapeutic agents against a wide variety of diseases.

A common mechanism links activities of butyrate in the colon

2017 ◽  
Author(s):  
Mohit S. Verma ◽  
Michael J. Fink ◽  
Gabriel L Salmon ◽  
Nadine Fornelos ◽  
Takahiro E. Ohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Histone Deacetylases ◽  
Biological Activities ◽  
Short Chain Fatty Acids ◽  
Common Mechanism ◽  
Epithelial Stem Cells ◽  
Degree Of Unsaturation ◽  
Structure Activity ◽  
Starting Point ◽  
New Compounds

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

Isothiocyanate Synthetic Analogs: Biological Activities, Structure-Activity Relationships and Synthetic Strategies

2014 ◽  
Vol 14 (12) ◽  
pp. 963-977 ◽  
Author(s):  
Andrea Milelli ◽  
Carmela Fimognari ◽  
Nicole Ticchi ◽  
Paolo Neviani ◽  
Anna Minarini ◽  
...  
Keyword(s):  
Biological Activities ◽  
Synthetic Analogs ◽  
Structure Activity Relationships ◽  
Structure Activity

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

scholarly journals Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 241
Author(s):  
Shaden A. M. Khalifa ◽  
Eslam S. Shedid ◽  
Essa M. Saied ◽  
Amir Reza Jassbi ◽  
Fatemeh H. Jamebozorgi ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Biomedical Applications ◽  
Large Scale ◽  
Biological Activities ◽  
Scale Production ◽  
Pharmacological Activities ◽  
Large Scale Production ◽  
Marine Products ◽  
Hiv 1 ◽  
Successful Phase

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

scholarly journals Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4312
Author(s):  
Benjamin Lefranc ◽  
Karima Alim ◽  
Cindy Neveu ◽  
Olivier Le Marec ◽  
Christophe Dubessy ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Pharmacological Profile ◽  
Acid Moiety ◽  
Structural Determinants ◽  
Physiological Processes ◽  
Structure Activity ◽  
Peptide Derivatives ◽  
Targeting Peptide ◽  
G Protein Coupled

26RFa is a neuropeptide that activates the rhodopsin-like G protein-coupled receptor QRFPR/GPR103. This peptidergic system is involved in the regulation of a wide array of physiological processes including feeding behavior and glucose homeostasis. Herein, the pharmacological profile of a homogenous library of QRFPR-targeting peptide derivatives was investigated in vitro on human QRFPR-transfected cells with the aim to provide possible insights into the structural determinants of the Phe residues to govern receptor activation. Our work advocates to include in next generations of 26RFa(20–26)-based QRFPR agonists effective substitutions for each Phe unit, i.e., replacement of the Phe22 residue by a constrained 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid moiety, and substitution of both Phe24 and Phe26 by their para-chloro counterpart. Taken as a whole, this study emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptide agonists for human QRFPR.

scholarly journals Green Silver and Gold Nanoparticles: Biological Synthesis Approaches and Potentials for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 844 ◽  
Author(s):  
Andrea Rónavári ◽  
Nóra Igaz ◽  
Dóra I. Adamecz ◽  
Bettina Szerencsés ◽  
Csaba Molnar ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Biomedical Applications ◽  
Biological Activities ◽  
Large Body ◽  
Chemical Properties ◽  
Biological Synthesis ◽  
Silver And Gold Nanoparticles ◽  
Comprehensive Collection ◽  
Synthetic Approaches ◽  
Physical And Chemical

The nanomaterial industry generates gigantic quantities of metal-based nanomaterials for various technological and biomedical applications; however, concomitantly, it places a massive burden on the environment by utilizing toxic chemicals for the production process and leaving hazardous waste materials behind. Moreover, the employed, often unpleasant chemicals can affect the biocompatibility of the generated particles and severely restrict their application possibilities. On these grounds, green synthetic approaches have emerged, offering eco-friendly, sustainable, nature-derived alternative production methods, thus attenuating the ecological footprint of the nanomaterial industry. In the last decade, a plethora of biological materials has been tested to probe their suitability for nanomaterial synthesis. Although most of these approaches were successful, a large body of evidence indicates that the green material or entity used for the production would substantially define the physical and chemical properties and as a consequence, the biological activities of the obtained nanomaterials. The present review provides a comprehensive collection of the most recent green methodologies, surveys the major nanoparticle characterization techniques and screens the effects triggered by the obtained nanomaterials in various living systems to give an impression on the biomedical potential of green synthesized silver and gold nanoparticles.

Synthesis and biological activities of chaetocin and its derivatives

2012 ◽  
Vol 84 (6) ◽  
pp. 1369-1378 ◽  
Author(s):  
Mikiko Sodeoka ◽  
Kosuke Dodo ◽  
Yuou Teng ◽  
Katsuya Iuchi ◽  
Yoshitaka Hamashima ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Caspase 3 ◽  
Biological Activities ◽  
Caspase 8 ◽  
Human Leukemia ◽  
Mechanistic Studies ◽  
Anticancer Activities ◽  
Histone Methyltransferases ◽  
Structure Activity ◽  
Apoptosis Inducer

Chaetocin, a natural product isolated from fungi of Chaetomium species, is a member of the epipolythiodiketopiperazines (ETPs), which have various biological activities, including cytostatic and anticancer activities. Recently, the inhibitory activity toward histone methyltransferases (HMTs) was discovered for chaetocin. We previously reported the first total synthesis of chaetocin and various derivatives. During studies on the structure–activity relationship for HMT inhibition, we found that the enantiomer of chaetocin (ent-chaetocin) is a more potent apoptosis inducer than natural chaetocin in human leukemia HL-60 cells. Mechanistic studies showed that ent-chaetocin induces apoptosis through the caspase-8/caspase-3 pathway.

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