scholarly journals IN SILICO STUDIES OF SOPHORAFLAVANONE G: QUANTUM CHARACTERIZATION AND ADMET

2020 ◽  
Vol 7 (11) ◽  
pp. 160-179 ◽  
Author(s):  
David Lopes Santiago De Oliveira ◽  
Emanuelle Machado Marinho ◽  
Francisco Nithael Melo Lucio ◽  
Marcia Machado Marinho ◽  
Francisco Rogênio Da Silva Mendes ◽  
...  
Keyword(s):  
Estrogen Receptor Alpha ◽  
Therapeutic Potential ◽  
Early Stage ◽  
Biological Activities ◽  
Three Dimensional ◽  
New Drugs ◽  
Dimensional Structure ◽  
Skin Permeability ◽  
Biological Targets ◽  
In Silico Studies

Currently, the search for new drugs with greater therapeutic potential and less side effects has been fostered by the advancement of the use of molecular modeling drugs, which in addition to supporting the full characterization of the molecule, allow simple algorithms to predict pharmacokinetic. In this context the present work aimed to perform the electronic / structural characterization, to evaluate the pharmacokinetic properties and to perform a virtual screening of the possible biological targets of Sophoraflavonone G, a promising flavonone, which presents several pharmacological properties. Sophoraflavanone G was geometrically optimized by semi-empirical quantum calculations, plot the MESP, identifying the nucleophilic sites. Using the boundary orbitals, it was possible to identify a greater tendency for electron donation in relation to Naringeni, with lower ionization potential, higher hardness and less softness. With respect to pharmacokinetics Sophoraflavonone G confirmed the safety of the compound for oral administration with good skin permeability, which allows applications in topical formulations. Presents indications for gastro intestinal absorption, as for possible interactions with biological targets, interaction with the estrogen receptor alpha, sodium / glucose co-transporter 2, beta-secretase 1, cyclooxygenase-1.The data obtained from an early stage for a comparative analysis between its analogues and fundamental for future studies of relationships between the three-dimensional structure of Sophoraflavanone G and its biological activities.

Phytochemical content and potential health applications of pecan [Carya illinoinensis (Wangenh) K. Koch] nutshell

2022 ◽  
Vol 22 ◽  
Author(s):  
Nohemí del C. Reyes-Vázquez ◽  
Laura A. de la Rosa ◽  
Juan Luis Morales-Landa ◽  
Jorge Alberto García-Fajardo ◽  
Miguel Ángel García-Cruz
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Heart Diseases ◽  
Extraction Methods ◽  
New Drugs ◽  
Potential Health ◽  
In Vivo Models ◽  
Phytochemical Content ◽  
Pecan Nutshell

Background: The pecan nutshell contains phytochemicals with various biological activities that are potentially useful in the prevention or treatment of diseases such as cancer, diabetes, and metabolic imbalances associated with heart diseases. Objective: To update this topic by means of a literature review and include those that contribute to the knowledge of the chemical composition and biological activities of pecan nutshell, particularly of those related to the therapeutic potential against some chronic degenerative diseases associated with oxidative stress. Method: Exhaustive and detailed review of the existing literature using electronic databases. Conclusion: The pecan nutshell is a promising natural product with pharmaceutical uses in various diseases. However, additional research related to the assessment of efficient extraction methods and characterization, particularly the evaluation of the mechanisms of action in new in vivo models, is necessary to confirm these findings and development of new drugs with therapeutic use.

scholarly journals TransformerCPI: improving compound–protein interaction prediction by sequence-based deep learning with self-attention mechanism and label reversal experiments

2020 ◽  
Vol 36 (16) ◽  
pp. 4406-4414 ◽  
Author(s):  
Lifan Chen ◽  
Xiaoqin Tan ◽  
Dingyan Wang ◽  
Feisheng Zhong ◽  
Xiaohong Liu ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Three Dimensional ◽  
Prediction Performance ◽  
Dimensional Structure ◽  
Sequence Information ◽  
Biological Targets ◽  
Interaction Prediction ◽  
Protein Interaction Prediction ◽  
Improved Performance ◽  
Ligand Bias

Abstract Motivation Identifying compound–protein interaction (CPI) is a crucial task in drug discovery and chemogenomics studies, and proteins without three-dimensional structure account for a large part of potential biological targets, which requires developing methods using only protein sequence information to predict CPI. However, sequence-based CPI models may face some specific pitfalls, including using inappropriate datasets, hidden ligand bias and splitting datasets inappropriately, resulting in overestimation of their prediction performance. Results To address these issues, we here constructed new datasets specific for CPI prediction, proposed a novel transformer neural network named TransformerCPI, and introduced a more rigorous label reversal experiment to test whether a model learns true interaction features. TransformerCPI achieved much improved performance on the new experiments, and it can be deconvolved to highlight important interacting regions of protein sequences and compound atoms, which may contribute chemical biology studies with useful guidance for further ligand structural optimization. Availability and implementation https://github.com/lifanchen-simm/transformerCPI.

scholarly journals Homology Modeling and Docking Studies of TMPRSS2 with Experimentally Known Inhibitors Camostat Mesylate, Nafamostat and Bromhexine Hydrochloride to Control SARS-Coronavirus-2

2020 ◽  
Author(s):  
Kailas Sonawane ◽  
Sagar S. Barale ◽  
Maruti J. Dhanavade ◽  
Shailesh R. Waghmare ◽  
Naiem H. Nadaf ◽  
...  
Keyword(s):  
Host Cell ◽  
Human Cell ◽  
Structural Information ◽  
Three Dimensional ◽  
Catalytic Triad ◽  
New Drugs ◽  
Dimensional Structure ◽  
Inhibition Mechanism ◽  
Global Public Health ◽  
Sars Coronavirus

The rapid outbreak of SARS-Coronavirus 2 (SARS-CoV-2) caused a serious global public health threat. The spike ‘S’ protein of SARS-CoV-2 and ACE2 of the host cell are being targeted to design and discover new drugs to control Covid-19 disease. Similarly, a transmembrane serine protease, TMPRSS2 of the host cell has been found to play a significant role in proteolytic cleavage of viral spike protein priming to the receptor ACE2 present in human cell. However, three dimensional structure and inhibition mechanism of TMPRSS2 is yet to be explored experimentally. Hence, in the present study we have generated a homology model of TMPRSS2 and studied its binding properties with experimentally studied inhibitors <i>viz.</i> Camostat mesylate, Nafamostat and Bromhexine hydrochloride (BHH) using molecular docking technique. Docking analysis revealed that the Camostat mesylate and its structural analogue Nafamostat interacts strongly with residues His296, Ser441 and Asp435 present in catalytic triad of TMPRSS2. However, BHH interacts with Gln438 and other residues present in the active site pocket of TMPRSS2 through hydrophobic contacts effectively. Thus, these results revealed the inhibition mechanism of TMPRSS2 by known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride in detail at the molecular level. However, Camostat mesylate shows strong binding as compared to other two inhibitors. This structural information could also be useful to design and discover new inhibitors of TMPRSS2, which may be helpful to prevent the entry to SARS-Coronavirus 2 in human cell.

Pharmaceutical interest of in-silico approaches

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Dinesh Kumar ◽  
Pooja Sharma ◽  
Ayush Mahajan ◽  
Ravi Dhawan ◽  
Kamal Dua
Keyword(s):  
Molecular Modeling ◽  
In Silico ◽  
Three Dimensional ◽  
Gene Sequencing ◽  
New Drugs ◽  
Dimensional Structure ◽  
Pharmaceutical Applications ◽  
Drug Designing ◽  
Different Types

Abstract The virtual environment within the computer using software performed on the computer is known as in-silico studies. These drugs designing software play a vital task in discovering new drugs in the field of pharmaceuticals. These designing programs and software are employed in gene sequencing, molecular modeling, and in assessing the three-dimensional structure of the molecule, which can further be used in drug designing and development. Drug development and discovery is not only a powerful, extensive, and an interdisciplinary system but also a very complex and time-consuming method. This book chapter mainly focused on different types of in-silico approaches along with their pharmaceutical applications in numerous diseases.

scholarly journals Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs.

1997 ◽  
Vol 41 (8) ◽  
pp. 1686-1692 ◽  
Author(s):  
A E Eakin ◽  
A Guerra ◽  
P J Focia ◽  
J Torres-Martinez ◽  
S P Craig
Keyword(s):  
Trypanosoma Cruzi ◽  
De Novo ◽  
Homo Sapiens ◽  
Three Dimensional ◽  
New Drugs ◽  
Dimensional Structure ◽  
Hypoxanthine Phosphoribosyltransferase ◽  
Inhibitor Design ◽  
Purine Nucleotides ◽  
Purine Analogs

The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi is a potential target for enzyme structure-based inhibitor design, based on previous studies which indicate that these parasites lack the metabolic enzymes required for de novo synthesis of purine nucleotides. By using a bacterial complement selection system, 59 purine analogs were assayed for their interaction with the HPRTs from T. cruzi and Homo sapiens. Eight compounds were identified from the bacterial assay to have an affinity for the trypanosomal enzyme. Inhibition constants for four of these compounds against purified recombinant trypanosomal and human HPRTs were determined and compared. The results confirm that the recombinant system can be used to identify compounds which have affinity for the trypanosomal HPRT. Furthermore, the results provide evidence for the importance of chemical modifications at positions 6 and 8 of the purine ring in the binding of these compounds to the HPRTs. An accurate three-dimensional structure of the trypanosomal enzyme will greatly enhance our understanding of the interactions between HPRTs and these compounds. Toward this end, crystallization conditions for the trypanosomal HPRT and preliminary analysis of X-ray diffraction data to a resolution of 2 A is reported. These results represent significant progress toward a structure-based approach to the design of inhibitors of the HPRT of trypanosomes with the long-range goal of developing new drugs for the treatment of Chagas' disease.

scholarly journals Synthesis and therapeutic potential of imidazole containing compounds

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ankit Siwach ◽  
Prabhakar Kumar Verma
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Properties ◽  
New Drugs ◽  
Hydrogen Atoms ◽  
Tautomeric Forms ◽  
Synthetic Routes ◽  
Derivatives Of ◽  
Heterocyclic Moiety ◽  
Antihistaminic Agent

Abstract Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857–1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.

scholarly journals On the Regularity of the Electron Configuration of Atoms in the Periodic Table

2021 ◽  
Vol 5 (2) ◽  
Keyword(s):  
Energy Level ◽  
Basic Principle ◽  
Periodic Table ◽  
Three Dimensional ◽  
Structural Formula ◽  
New Drugs ◽  
Dimensional Structure ◽  
Electron Configuration ◽  
Transition Elements ◽  
Three Dimensional Structure

The current periodic table does not necessarily have a clear position for transition elements. Therefore, the purpose of this paper is to use the basic principle discovered by Mendeleev as it is and to create a periodic table with consistency for transition elements. By setting some hypotheses, it was found that transition elements also have regular periodicity, so we succeeded in clarifying the energy level of electrons in each orbit. In addition, by utilizing its periodicity, the electron configuration for each orbit was predicted for unknown elements. In this paper, we did not take the conventional idea of electron orbitals, that is, the idea of forming a hybrid orbital, but assumed a new orbital. Since the state in which electrons fit in orbits and stabilize is defined as an octet, this idea was used as the basic principle in this paper, but the hypothesis that "there are only three orbits in each shell" was established and verified. The calculation of the energy level of the electrons on the orbit became extremely easy, and the order of each orbit could be clarified. It was also found that the three-dimensional structure of the molecule may be visualized by paying attention to the valence electrons of the outermost shell of the element and the octet of the stability condition. Therefore, in this paper, by slightly expanding the structural formula of Kekulé, it became possible to easily determine whether or not the molecule synthesized by the bond between elements is stable. In addition, it has become possible to predict the three-dimensional structure of the molecule as well. Furthermore, not only will it be easier for students studying chemistry to understand complex chemical reactions, but it will also be useful for researchers in the development and research of new drugs.

scholarly journals Therapeutic potential of oxadiazole or furadiazole containing compounds

BMC Chemistry ◽  
2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ankit Siwach ◽  
Prabhakar Kumar Verma
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Antiviral Drug ◽  
Biological Properties ◽  
New Drugs ◽  
Pharmacological Activities ◽  
Methylene Groups ◽  
Synthetic Routes ◽  
Azole Ring ◽  
Derivatives Of

AbstractAs we know that, Oxadiazole or furadi azole ring containing derivatives are an important class of heterocyclic compounds. A heterocyclic five-membered ring that possesses two carbons, one oxygen atom, two nitrogen atoms, and two double bonds is known as oxadiazole. They are derived from furan by the replacement of two methylene groups (= CH) with two nitrogen (-N =) atoms. The aromaticity was reduced with the replacement of these groups in the furan ring to such an extent that it shows conjugated diene character. Four different known isomers of oxadiazole were existed such as 1,2,4-oxadiazole, 1,2,3-oxadiazole, 1,2,5-oxadiazole & 1,3,4-oxadiazole. Among them, 1,3,4-oxadiazoles & 1,2,4-oxadiazoles are better known and more widely studied by the researchers due to their broad range of chemical and biological properties. 1,3,4-oxadiazoles have become important synthons in the development of new drugs. The derivatives of the oxadiazole nucleus (1,3,4-oxadiazoles) show various biological activities such as antibacterial, anti-mycobacterial, antitumor, anti-viral and antioxidant activity, etc. as reported in the literature. There are different examples of commercially available drugs which consist of 1,3,4-oxadiazole ring such as nitrofuran derivative (Furamizole) which has strong antibacterial activity, Raltegravir as an antiviral drug and Nesapidil drug is used in anti-arrhythmic therapy. This present review summarized some pharmacological activities and various kinds of synthetic routes for 2, 5-disubstituted 1,3,4-oxadiazole, and their derived products.

Observation of Aneurobracon philippinensis (Hymenoptera: Braconidae) Immatures Shows How Koinobiont Offspring Flexibly Adjust Their Development to Host Growth

2019 ◽  
Vol 112 (5) ◽  
pp. 490-496 ◽  
Author(s):  
Haruka Aoyama ◽  
Issei Ohshima
Keyword(s):  
Developmental Stages ◽  
Early Stage ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
First Instar ◽  
Leaf Mining ◽  
Wild Host ◽  
Host Growth ◽  
In The Wild ◽  
The Ideal

AbstractKoinobionts are parasitoids that allow their hosts to grow after infection, and they finally kill their host individuals at parasitoid-specific host stages. Since fatal accidents of host organisms directly result in the deaths of parasitizing koinobionts, a longer parasitization period in vulnerable hosts is likely to increase the mortality of the koinobionts. However, for hosts inhabiting concealed environments in their later developmental stages, koinobionts should begin parasitization in early-stage hosts to make use of the grown hosts. A koinobiont parasitoid, Aneurobracon philippinensis (Muesebeck), mainly uses a leaf-mining moth, Acrocercops transecta Meyrick (Lepidoptera: Gracillariidae) as a host. Due to the three-dimensional structure of the mines constructed by later instars of A. transecta, females of A. philippinensis seldomly oviposit into later instar hosts, whereas feeding on final instar hosts is essential for A. philippinensis larvae. This implies that oviposition targets in the wild are shifted to early instars, though the final instar is the ideal target to shorten the parasitization period. The dissection of wild host larvae demonstrated that no eggs were observed in the final instar, supporting the above expectation. Laboratory parasitization experiments revealed that A. philippinensis eggs hatched approximately 80 h after oviposition, and hatched larvae stayed in the first instar until the host larvae completed making cocoons. These results suggest that the first-instar period of the parasitoid larvae functions as an adjusting period to synchronize the parasitoid and host developmental stages and that koinobiosis plays an important role in utilizing the final instar of A. transecta as a resource.

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