scholarly journals Drug discovery for hearing loss: Phenotypic screening of chemical compounds on primary cultures of the spiral ganglion

2017 ◽  
Vol 349 ◽  
pp. 177-181 ◽  
Author(s):  
Donna S. Whitlon
Keyword(s):  
Hearing Loss ◽  
Drug Discovery ◽  
Primary Cultures ◽  
Spiral Ganglion ◽  
Chemical Compounds ◽  
Phenotypic Screening

Secondary Metabolites of Plant Origin containing Carbazole as Lead Molecule: A Review

2019 ◽  
Vol 05 ◽  
Author(s):  
Atul Sharma ◽  
Devender Pathak
Keyword(s):  
Drug Discovery ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Chemical Compounds ◽  
Lethal Effect ◽  
Chemical Diversity ◽  
Chemical Transformations ◽  
Pharmacological Effects ◽  
Structural Class ◽  
Biological Targets

Keeping this fact that study of a body is biology but life is all about chemicals and chemical transformations, many medicinal chemist start research in finding new and novel chemical compounds which having pharmacological activities. Most of those chemical compounds which are having active pharmacological effects are heterocyclic compounds. Heterocyclic compounds clutch a particular place among pharmaceutically active natural and synthetic compounds. The ability to serve both as biomimetics and reactive pharmacophores of heterocyclic nuclei is incredible and it has principally contributed to their unique value as traditional key elements of numerous drugs. These heterocyclic nuclei offer a huge area for new lead molecules for drug discovery and for generation of activity relationships with biological targets to enhance pharmacological effects. For these reasons, it is not surprising that this structural class has received special attention in drug discovery. The hydrogen bond acceptors and donors arranged in a manner of a semi-rigid skeleton in heterocyclic rings and therefore they can present a varied display of significant pharmacophores. Lead identification and optimization of drug target probable can be achieved by generation of chemical diversity produced by derivatization of heterocyclic pharmacophores with different groups or substituents. A tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various potential biological activities such as anticancer, antimicrobial and antiviral. Binding mechanism of carbazole with target receptor as a molecule or fused molecule exhibits the potential lethal effect.

scholarly journals ChemBioServer 2.0: an advanced web server for filtering, clustering and networking of chemical compounds facilitating both drug discovery and repurposing

2020 ◽  
Vol 36 (8) ◽  
pp. 2602-2604 ◽  
Author(s):  
Evangelos Karatzas ◽  
Juan Eiros Zamora ◽  
Emmanouil Athanasiadis ◽  
Dimitris Dellis ◽  
Zoe Cournia ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Perfect Match ◽  
Web Server ◽  
Drug Repurposing ◽  
Chemical Compounds ◽  
Structural Similarity ◽  
Substructure Search ◽  
Similarity Network ◽  
Compound Libraries ◽  
Network Analysis Metrics

Abstract Summary ChemBioServer 2.0 is the advanced sequel of a web server for filtering, clustering and networking of chemical compound libraries facilitating both drug discovery and repurposing. It provides researchers the ability to (i) browse and visualize compounds along with their physicochemical and toxicity properties, (ii) perform property-based filtering of compounds, (iii) explore compound libraries for lead optimization based on perfect match substructure search, (iv) re-rank virtual screening results to achieve selectivity for a protein of interest against different protein members of the same family, selecting only those compounds that score high for the protein of interest, (v) perform clustering among the compounds based on their physicochemical properties providing representative compounds for each cluster, (vi) construct and visualize a structural similarity network of compounds providing a set of network analysis metrics, (vii) combine a given set of compounds with a reference set of compounds into a single structural similarity network providing the opportunity to infer drug repurposing due to transitivity, (viii) remove compounds from a network based on their similarity with unwanted substances (e.g. failed drugs) and (ix) build custom compound mining pipelines. Availability and implementation http://chembioserver.vi-seem.eu.

scholarly journals Next-Generation Phenotypic Screening in Early Drug Discovery for Infectious Diseases

2019 ◽  
Vol 35 (7) ◽  
pp. 559-570 ◽  
Author(s):  
Nathalie Aulner ◽  
Anne Danckaert ◽  
JongEun Ihm ◽  
David Shum ◽  
Spencer L. Shorte
Keyword(s):  
Drug Discovery ◽  
Infectious Diseases ◽  
Phenotypic Screening ◽  
Next Generation ◽  
Early Drug

scholarly journals Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons

2020 ◽  
Vol 14 ◽  
Author(s):  
Francis Rousset ◽  
Vivianne B. C. Kokje ◽  
Rebecca Sipione ◽  
Dominik Schmidbauer ◽  
German Nacher-Soler ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Progenitor Cells ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Specific Cell ◽  
Auditory Neurons ◽  
Self Renewal ◽  
Starting Point ◽  
Ganglion Neurons

Nearly 460 million individuals are affected by sensorineural hearing loss (SNHL), one of the most common human sensory disorders. In mammals, hearing loss is permanent due to the lack of efficient regenerative capacity of the sensory epithelia and spiral ganglion neurons (SGN). Sphere-forming progenitor cells can be isolated from the mammalian inner ear and give rise to inner ear specific cell types in vitro. However, the self-renewing capacities of auditory progenitor cells from the sensory and neuronal compartment are limited to few passages, even after adding powerful growth factor cocktails. Here, we provide phenotypical and functional characterization of a new pool of auditory progenitors as sustainable source for sphere-derived auditory neurons. The so-called phoenix auditory neuroprogenitors, isolated from the A/J mouse spiral ganglion, exhibit robust intrinsic self-renewal properties beyond 40 passages. At any passage or freezing–thawing cycle, phoenix spheres can be efficiently differentiated into mature spiral ganglion cells by withdrawing growth factors. The differentiated cells express both neuronal and glial cell phenotypic markers and exhibit similar functional properties as mouse spiral ganglion primary explants and human sphere-derived spiral ganglion cells. In contrast to other rodent models aiming at sustained production of auditory neurons, no genetic transformation of the progenitors is needed. Phoenix spheres therefore represent an interesting starting point to further investigate self-renewal in the mammalian inner ear, which is still far from any clinical application. In the meantime, phoenix spheres already offer an unlimited source of mammalian auditory neurons for high-throughput screens while substantially reducing the numbers of animals needed.

Secondary metabolites of the genus Crotalaria (Rattlepods) and their medicinal importance – A review

2020 ◽  
pp. 1-7
Author(s):  
Muhammad Sarwar Yaqub ◽  
Bushra Basher ◽  
Rozina Aslam
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acids ◽  
Wound Healing ◽  
Drug Discovery ◽  
Secondary Metabolites ◽  
Metabolic Pathways ◽  
Growth And Development ◽  
Chemical Compounds ◽  
Diverse Group ◽  
The World

This review describes the genus Crotalaria focusing on its secondary metabolites and their medicinal applications. The genus Crotalaria of Fabaceae or Leguminosae family have about 600 species which are distributed in tropic and sub-tropic regions of the world. They are medicinally important due to production of various compounds. Traditional early medicines and drug discovery were based on natural products. Organisms produce some chemical compounds by their metabolic pathways that are not necessary for their growth and development and are known as secondary metabolites. This diverse group of compounds is synthesized by algae, plants, animals and fungi. These metabolites consist of variety of compounds such as phenols, coumarins, terpenoids, flavonoids, alkaloids, steroids and fatty acids. Secondary metabolites obtained from crotalaria exhibit anticancer, anti-rheumatoid arthritis, anti-allergic, antioxidant, antimicrobial, antiaging and wound healing activities along with many other medicinal applications.

Survival of Spiral Ganglion Cells in Profound Sensorineural Hearing Loss: Implications for Cochlear Implantation

1989 ◽  
Vol 98 (6) ◽  
pp. 411-416 ◽  
Author(s):  
Joseph B. Nadol ◽  
Yi-Shyang Young ◽  
Robert J. Glynn
Keyword(s):  
Hearing Loss ◽  
Ganglion Cell ◽  
Cell Count ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Bivariate Analysis ◽  
Spiral Ganglion Cell ◽  
Cell Counts ◽  
Profound Deafness ◽  
Temporal Bones

Ninety-three temporal bones from 66 patients who were profoundly deaf during life were reconstructed by analysis of serial light microscopic sections. The correlations of total and segmental spiral ganglion cell counts with age, duration of hearing loss and profound deafness, and cause of hearing loss were evaluated. Bivariate analysis demonstrated that total spiral ganglion cell count tended to be lower in older than in younger deaf individuals and lower with longer duration of hearing loss and total deafness. However, multiple regression analysis demonstrated that the cause of hearing loss was the single most significant determinant of total spiral ganglion cell count. Patients with deafness due to aminoglycoside toxicity or sudden idiopathic deafness had the highest residual spiral ganglion cell count and patients with deafness due to presumptive postnatal viral labyrinthitis, bacterial labyrinthitis, and congenital or genetic causes had the lowest numbers of residual spiral ganglion cells.

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