Best possible natural ligands which were enlisted on NPACT website were screened ( aid of major drug likeness parameters - pkCSM) and docked with the 2OJG(Target protein) using autodock.
This is the PowerPoint presentation by extracting data from a research article. This is the title of article" Augmented CO2 tolerance by expressing a single H+-pump enables microalgal valorization of industrial flue gas" published in nature communications. You can download it and ask me to provide you this article as well.
Determination of 8-Hydroxy-2 Deoxyguanosine in Pseudomonas Fluorescens Freeze...Agriculture Journal IJOEAR
Abstract— Oxidative DNA damage is involved in the f cell death induced by freeze-dried powder during storage. Cell 8-hydroxy-2’deoxyguanosine (8-oxodG) is widely accepted as a biomarker of the “freeze-dried bacteria” oxidative DNA damage. The aim of this study was to introduce a method for determination 8-oxodG in cell freeze-dried samples using high-performance liquid chromatography with electrochemical detection. In the tested range of 0.5 µmol L-1 to 1.0 nmol L-1, the calibration curve was linear (r2=0.9995) and the limit of detection was 0.05 µmol L-1. The used method did not allow highlighting the presence in the samples of the 8OH within the limits of detection. A more successful method (more sensitive) would be needed to detect possibly the 8OH.
Comprehensive Investigation of the Utilization of SFC/ESI Positive Mode MS fo...Waters Corporation
Bioanalysis and drug metabolism studies are critical parts of the drug development process. The aim of these studies is to identify and quantify drugs and their associated metabolites in biofluids such as plasma and urine. Typically reversed-phase chromatography coupled with mass spectrometry is often the analytical technique of choice utilized in the analyses due to the specificity and sensitivity of the technique. However, due to the complexity of the biofluid samples accurate and precise measurements can become challenging due to poor chromatographic peak shape, insufficient chromatographic resolution from matrix components and incompatible sample compositions.
Recent advancements in the field of super critical fluid chromatography (SFC) have lead to the development of sub 2 micron chromatographic separations coupled mass spectrometry operating under positive ESI mode. In the work presented here the applicability of SFC for both chiral and achiral bioanalysis is shown. The orthogonal separation selectivity compared with reversed-phase separations and tolerance for high organic sample compositions will be discussed. This work further presents a critical evaluation of the influence of mobile phase and make up flow modifiers on the sensitivity and selectivity of probe pharmaceuticals analyzed under SFC/ESI positive mode MS conditions.
Paul Rainville of Waters Corporation gave this Oral presentation at Pittcon 2015.
Antioxidant biosensor based on D. radiodurans biofilm has been investigated in this research. The biofilm producing SOD enzymes were immobilized on SPCE surface. Optimization of experimental measurements were carried out by the response surface method. The optimum value obtained was at the buffer pH 7, suspension pH 6, and optical density (OD) 0.5. The morphology of SPCE surfaces was characterized by SEM. The optimum result was used to determinate analytical performance, including linearity, sensitivity, limit of detection (LOD), limit of quantity (LOQ), precision, selectivity, stability, and repeatability. Linearity was achieved in the xanthine concentration range of 0.1-0.6 mM with the equation y = 40.79x + 57.173 and R² = 0.99. The apparent Michaelis-Menten constant KMwas evaluated. It was found that the biosensor had alow KMof 40 μM. LOD and LOQ respectively 40.8 μM and 123.7 μM with sensitivity 40.79 μA mM-1. Precision showed that RSD was less than 5%. Stability was measured for 35 days andretained 90% of current for the period. Repeatability showedRSD ≤ 5%. The selectivity of this method still needs to increase. In conclusion, antioxidant biosensor based on D. radioduransbiofilm may be used to measure the capacity of antioxidant products practically.
I presented two fascinating stories where Molecular Dynamics simulations contributed to enhancing our understanding of immunodeficiencies. In one of the projects, the treatment of patients could be improved. These slides were presented at the Basler Modeller Stammtisch, 26.02.2021
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
This is the PowerPoint presentation by extracting data from a research article. This is the title of article" Augmented CO2 tolerance by expressing a single H+-pump enables microalgal valorization of industrial flue gas" published in nature communications. You can download it and ask me to provide you this article as well.
Determination of 8-Hydroxy-2 Deoxyguanosine in Pseudomonas Fluorescens Freeze...Agriculture Journal IJOEAR
Abstract— Oxidative DNA damage is involved in the f cell death induced by freeze-dried powder during storage. Cell 8-hydroxy-2’deoxyguanosine (8-oxodG) is widely accepted as a biomarker of the “freeze-dried bacteria” oxidative DNA damage. The aim of this study was to introduce a method for determination 8-oxodG in cell freeze-dried samples using high-performance liquid chromatography with electrochemical detection. In the tested range of 0.5 µmol L-1 to 1.0 nmol L-1, the calibration curve was linear (r2=0.9995) and the limit of detection was 0.05 µmol L-1. The used method did not allow highlighting the presence in the samples of the 8OH within the limits of detection. A more successful method (more sensitive) would be needed to detect possibly the 8OH.
Comprehensive Investigation of the Utilization of SFC/ESI Positive Mode MS fo...Waters Corporation
Bioanalysis and drug metabolism studies are critical parts of the drug development process. The aim of these studies is to identify and quantify drugs and their associated metabolites in biofluids such as plasma and urine. Typically reversed-phase chromatography coupled with mass spectrometry is often the analytical technique of choice utilized in the analyses due to the specificity and sensitivity of the technique. However, due to the complexity of the biofluid samples accurate and precise measurements can become challenging due to poor chromatographic peak shape, insufficient chromatographic resolution from matrix components and incompatible sample compositions.
Recent advancements in the field of super critical fluid chromatography (SFC) have lead to the development of sub 2 micron chromatographic separations coupled mass spectrometry operating under positive ESI mode. In the work presented here the applicability of SFC for both chiral and achiral bioanalysis is shown. The orthogonal separation selectivity compared with reversed-phase separations and tolerance for high organic sample compositions will be discussed. This work further presents a critical evaluation of the influence of mobile phase and make up flow modifiers on the sensitivity and selectivity of probe pharmaceuticals analyzed under SFC/ESI positive mode MS conditions.
Paul Rainville of Waters Corporation gave this Oral presentation at Pittcon 2015.
Antioxidant biosensor based on D. radiodurans biofilm has been investigated in this research. The biofilm producing SOD enzymes were immobilized on SPCE surface. Optimization of experimental measurements were carried out by the response surface method. The optimum value obtained was at the buffer pH 7, suspension pH 6, and optical density (OD) 0.5. The morphology of SPCE surfaces was characterized by SEM. The optimum result was used to determinate analytical performance, including linearity, sensitivity, limit of detection (LOD), limit of quantity (LOQ), precision, selectivity, stability, and repeatability. Linearity was achieved in the xanthine concentration range of 0.1-0.6 mM with the equation y = 40.79x + 57.173 and R² = 0.99. The apparent Michaelis-Menten constant KMwas evaluated. It was found that the biosensor had alow KMof 40 μM. LOD and LOQ respectively 40.8 μM and 123.7 μM with sensitivity 40.79 μA mM-1. Precision showed that RSD was less than 5%. Stability was measured for 35 days andretained 90% of current for the period. Repeatability showedRSD ≤ 5%. The selectivity of this method still needs to increase. In conclusion, antioxidant biosensor based on D. radioduransbiofilm may be used to measure the capacity of antioxidant products practically.
I presented two fascinating stories where Molecular Dynamics simulations contributed to enhancing our understanding of immunodeficiencies. In one of the projects, the treatment of patients could be improved. These slides were presented at the Basler Modeller Stammtisch, 26.02.2021
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Toxic effects of heavy metals : Lead and Arsenicsanjana502982
Heavy metals are naturally occuring metallic chemical elements that have relatively high density, and are toxic at even low concentrations. All toxic metals are termed as heavy metals irrespective of their atomic mass and density, eg. arsenic, lead, mercury, cadmium, thallium, chromium, etc.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
DERIVATION OF MODIFIED BERNOULLI EQUATION WITH VISCOUS EFFECTS AND TERMINAL V...Wasswaderrick3
In this book, we use conservation of energy techniques on a fluid element to derive the Modified Bernoulli equation of flow with viscous or friction effects. We derive the general equation of flow/ velocity and then from this we derive the Pouiselle flow equation, the transition flow equation and the turbulent flow equation. In the situations where there are no viscous effects , the equation reduces to the Bernoulli equation. From experimental results, we are able to include other terms in the Bernoulli equation. We also look at cases where pressure gradients exist. We use the Modified Bernoulli equation to derive equations of flow rate for pipes of different cross sectional areas connected together. We also extend our techniques of energy conservation to a sphere falling in a viscous medium under the effect of gravity. We demonstrate Stokes equation of terminal velocity and turbulent flow equation. We look at a way of calculating the time taken for a body to fall in a viscous medium. We also look at the general equation of terminal velocity.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
1. DRUG LIKENESS AND MOLECULAR
DOCKING ANALYSIS OF MAPK
INHIBITORS FROM THE NPACT
DATABASE
Department of Pharmacology
K.K. COLLEGE OF PHARMACY, CHENNAI 600122
Presented By
SAMSON RAJ Y SAVITHA C SANTHOSH M
Under the guidance of Prof. Dr. B. Premkumar, M. Pharm., Ph.D., Head of the Department
2. INTRODUCTION
2
Melanoma is identified as one of the most dangerous forms of the skin
tumor, having quick metastasizing, progression and a high burden of death.
Even though a significant figure of therapies has been established recently for the late-
stage melanoma cancer, this disease has not been defeated yet; resistance develops
through cancer heterogeneity
This study has been designed to explore the anticancer potential of NPACT ligands
against the Mitogen Activated Protein Kinase (MAPK) signaling in melanoma. The
hit compounds obtained in this study could play an important role in designing
personalized therapy against melanoma patients.
3. AIM
3
• To find the potential ligands for the paramount cancer type “Melanoma” (skin
cancer) with the target receptor being chosen from research articles and utilizing it
for computational screening of natural ligands submitted in NPACT site.
• In silico screening approaches has been applied to find the suitable ligand, which
can be treated for further studies.
4. OBJECTIVES
4
Selection of the macromolecule
Obtaining the 3D protein structure from protien data bank.
Determination of grid specification (using Biovia discovery studio)
Retrieval of natural ligands from NPACT site.
Processing of ligands (using Marvin sketch).
Analysis of ADMET properties (using pkCSM online tool).
Performing docking (Autodock vina 1.2.3)
Hierarchical determination of ligands.
Tabulation and interpretation of results.
6. Determination of target receptor
6
• The transferase 2OJG [Mitogen-activated protein kinase 1] (UNIPORT ID: P28482)
was found one of the most commonly protein worked in Melanoma in correlation with
computational screening to a potential target protein.
• Additionally, 2OJG is single chain interacting protein and free from mutation, it is
more efficient to work.
7. Retrieval & Processing of protein
7
• The transferase Melanoma protein 2OJG is found to be submitted as crystal structure
of ERK2 (gene name) in complex with ‘19A’ and SO4.
• For effective docking additive molecules (19A, SO4, water) are removed from the
macromolecule and making the binding pocket available, by using Discovery studio-
Biovia.
• Required charge were added to the target protein (Kolmann charges) along with
addition of hydrogen bonds and pairing of polar bonds. Obtaining the protein as ready
to dock in PDBQT format.
8. Retrieval & Processing of ligands
8
• The NPACT ligand molecules were obtained and screened for potential ligands by
placing parameters such as Lipinski’s rule of five, Ghose filter, Veber filter,
Muegge Filter, Hepatotoxicity.
• Molecular descriptors were noted for the selected ligand molecules
• Ligand molecules were obtained from NPACT site in MOL2 format which was
converted to 3D structures in Marvin Sketch
• Followed by obtaining the ligands as PDBQT format using Auto dock Racoon
which included addition of torsion and charges to the selected ligands.
9. Analysis of ADMET properties
9
The sorted compounds were further analyzed for ADMET properties
• Absorption: Water solubility, Caco-2 permeability, Substrate of P glycoprotein,
• Distribution: Volume of distribution, Blood Brain Barrier permeability, CNS
permeability.
• Metabolism: CYP2D6 substrate, CYP3A4 substrate.
• Excretion: Total Clearance, Renal OCT2 substrate.
• Toxicity: AMES toxicity, Max. Tolerated dose (human), hERG I inhibitor, hERG II
inhibitor, Oral Rat Acute Toxicity, Hepatoxicity
10. Performing docking
10
• The ready to dock files (i.e. target protein and ligands in PDBQT format) were utilized
for docking.
• Grid configurations are determined with the aid of Native ligand of submitted protein
grid size was set to 60 x 60 x 60 x y z points with grid spacing (0.375) and the grid
center was designated at dimensions (x y z as 13.88, 13.865, 41.85 respectively)
• Ligand were bound with the protein with the aid of AutoDock vina 1.2.3.
11. Results
11
• Out of 1574 compounds 464 ligands were chosen molecular docking was carried out on
batch basis using AutoDock vina 1.2.3., Compounds were ranked on basis of least
binding energy.
• All the candidate compounds were subjected to pkCSM online tool to assess them for
their drug like properties, server in order to further validate the potential of drug
likeliness.
13. 13
MOLECULAR
DESCRIPTOR
Sulfuretin Sumatrol Taiwaniaquinol
A
Epicatec
hin
Parthenolide Piceatannol Tectorigenin Strychnine Viscidulin Methoxypraecansone
ABSORPTION
Water solubility
(logmol/L)
-2.899 -4.852 -5.146 -3.117 -3.161 -3.227 -3.435 -3.445 -3.341 -5.591
Caco2
permeability
1.208 1.48 1.721 -0.283 1.71 0.878 -0.132 1.56 -0.003 1.064
Intestinal
absorption
(human)
89.347 94.671 93.195 68.829 97.599 88.197 84.511 99.843 81.929 95.845
P-glycoprotein
substrate (Y/N)
Yes No No Yes No Yes Yes Yes Yes No
Molecular descriptors for the top ligand molecules predicted using pkCSM online tool
14. 14
MOLECULAR
DESCRIPTOR
Sulfuretin Sumatrol Taiwaniaquinol
A
Epicatec
hin
Parthenolide Piceatannol Tectorigenin Strychnine Viscidulin Methoxypraecansone
DISTRIBUTION
VDSS(human,log
L/Kg)
0.479 -0.156 0.425 1.027 0.291 0.438 0.166 1.16 0.161 0.195
BBB permeability -0.706 -0.714 -0.678 -1.054 0.444 -0.776 -1.06 0.148 -1.31 -0.45
CNS permeability -2.203 -2.955 -1.673 -3.298 -3.007 -2.257 -2.404 -2.165 -3.403 -1.972
METABOLISM
CYP2D6 inhibitor No No No No No No No No No No
CYP3A4 inhibitor No Yes No No No Yes Yes Yes Yes Yes
15. 15
MOLECULAR
DESCRIPTOR
Sulfuretin Sumatrol Taiwaniaquinol
A
Epicatec
hin
Parthenolide Piceatannol Tectorigenin Strychnine Viscidulin Methoxypraecansone
EXCREATION
Total
clearance(logml/m
in/kg)
-0.042 0.244 0.235 0.183 1.162 0.004 0.132 0.965 0.237 0.305
Renal OCT2
substrate(Y/N)
No No No No Yes No No Yes No Yes
TOXICITY
AMES
Toxicity(Y/N)
No No No No No No No No No No
Max.tolerated
dose(human,logm
g/kg/day)
-0.185 0.348 -0.459 0.438 0.306 0.338 0.334 -0.535 0.354 0.53
HERG 1 inhibitor No No No No No No No No No No
HERG 2 inhibitor No No No No No No No Yes No Yes
Hepatotoxicity No No No No No No No No No No
Oral rat acute
toxicity (LD50)
2.42 2.476 2.577 2.482 2.096 2.529 2.33 2.798 2.195 2.535
17. 17
A
Depiction of molecular interaction of target receptor (protein) on forming complexes with
sulfuretin, using LigPlot
18. 18
B
Depiction of molecular interaction of target receptor (protein) on forming complexes with
sumetrol using LigPlot
19. Conclusion
19
• The current study investigated the potential of natural ligands as useful ligands in
melanoma drug discovery and druggable candidates are listed down.
• The filtered drug-like natural compounds (ADMET properties and Lipinski’s rule
of five) were taken forward to discover potential inhibitors against the target
protein.
• These outcomes endorsed that the most active candidates Sulfuretin, Sumetrol,
Taiwaniaquinol A may serve as useful lead compounds in the search for
promising anti-melanoma agents acting through MAPK-inhibition.