scholarly journals THEORETICAL APPROACH ON TARGETING PLANT FUNGAL PATHOGENIC PROTEINS AGAINST NATURALLY ISOLATED COMPOUNDS FROM CHITINIPHILUS SHINANONENSIS

2019 ◽  
pp. 138-142
Author(s):  
KRITHIKA S ◽  
CHELLARAM C
Keyword(s):  
Drug Targets ◽  
Fungal Pathogens ◽  
Interaction Analysis ◽  
Pathogenic Fungus ◽  
Three Dimensional ◽  
Data Bank ◽  
Asiatic Acid ◽  
Literature Study

Objective: The objective of this study was to find the potency and bioefficacy of Asiatic acid and triterpene against four different plant fungal pathogens using a structure-based drug designing approach. Methods: The pathogenic fungus which causes a dreadful effect on plants is reviewed from literature study, and its three-dimensional structures are retrieved from the protein data bank database. On the other hand, ligands are prepared. Finally, prepared fungal drug targets are docked with naturally isolated compounds using AutoDock tools. Results: Both compounds Asiatic acid and triterpene structures are complementary to bind at the active site of four different drug targets. Comparatively, it is more favorable for Avr2 effector protein from Fusarium oxysporum with Ki value of 126.60 μM, 1.76 μM, and dock score value of −5.32 kcal/mol and −7.85 kcal/mol for Asiatic acid and triterpene, respectively. Thus, interaction analysis was carried out only for these protein-ligand complexes. Conclusion: The computational biology study states that these two compounds can be the lead candidate for treating disease caused by plant fungal pathogen F. oxysporum. However, further study has to be done in vitro and in vivo to prove its same efficacy.

scholarly journals BanLec-eGFP Chimera as a Tool for Evaluation of Lectin Binding to High-Mannose Glycans on Microorganisms

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 180
Author(s):  
Zorana Lopandić ◽  
Luka Dragačević ◽  
Dragan Popović ◽  
Uros Andjelković ◽  
Rajna Minić ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Lectin Binding ◽  
Three Dimensional ◽  
Data Bank ◽  
Salmonella Typhi ◽  
Excitation Wavelength ◽  
Protein Data Bank Entry ◽  
High Mannose

Fluorescently labeled lectins are useful tools for in vivo and in vitro studies of the structure and function of tissues and various pathogens such as viruses, bacteria, and fungi. For the evaluation of high-mannose glycans present on various glycoproteins, a three-dimensional (3D) model of the chimera was designed from the crystal structures of recombinant banana lectin (BanLec, Protein Data Bank entry (PDB): 5EXG) and an enhanced green fluorescent protein (eGFP, PDB 4EUL) by applying molecular modeling and molecular mechanics and expressed in Escherichia coli. BanLec-eGFP, produced as a soluble cytosolic protein of about 42 kDa, revealed β-sheets (41%) as the predominant secondary structures, with the emission peak maximum detected at 509 nm (excitation wavelength 488 nm). More than 65% of the primary structure was confirmed by mass spectrometry. Competitive BanLec-eGFP binding to high mannose glycans of the influenza vaccine (Vaxigrip®) was shown in a fluorescence-linked lectin sorbent assay (FLLSA) with monosaccharides (mannose and glucose) and wild type BanLec and H84T BanLec mutant. BanLec-eGFP exhibited binding to mannose residues on different strains of Salmonella in flow cytometry, with especially pronounced binding to a Salmonella Typhi clinical isolate. BanLec-eGFP can be a useful tool for screening high-mannose glycosylation sites on different microorganisms.

scholarly journals Novel Bioengineered Three-Dimensional Human Intestinal Model for Long-Term Infection of Cryptosporidium parvum

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Maria A DeCicco RePass ◽  
Ying Chen ◽  
Yinan Lin ◽  
Wenda Zhou ◽  
David L. Kaplan ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Drug Targets ◽  
Diarrheal Disease ◽  
Three Dimensional ◽  
Content Type ◽  
Tissue Model ◽  
Culture Models

ABSTRACT Cryptosporidium spp. are apicomplexan parasites of global importance that cause human diarrheal disease. In vitro culture models that may be used to study this parasite and that have physiological relevance to in vivo infection remain suboptimal. Thus, the pathogenesis of cryptosporidiosis remains poorly characterized, and interventions for the disease are limited. In this study, we evaluated the potential of a novel bioengineered three-dimensional (3D) human intestinal tissue model (which we developed previously) to support long-term infection by Cryptosporidium parvum. Infection was assessed by immunofluorescence assays and confocal and scanning electron microscopy and quantified by quantitative reverse transcription-PCR. We found that C. parvum infected and developed in this tissue model for at least 17 days, the extent of the study time used in the present study. Contents from infected scaffolds could be transferred to fresh scaffolds to establish new infections for at least three rounds. Asexual and sexual stages and the formation of new oocysts were observed during the course of infection. Additionally, we observed ablation, blunting, or distortion of microvilli in infected epithelial cells. Ultimately, a 3D model system capable of supporting continuous Cryptosporidium infection will be a useful tool for the study of host-parasite interactions, identification of putative drug targets, screening of potential interventions, and propagation of genetically modified parasites.

scholarly journals iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio055087
Author(s):  
Igor Gurevich ◽  
Sarah A. Burton ◽  
Christie Munn ◽  
Makiko Ohshima ◽  
Madelyn E. Goedland ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Drug Targets ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Alcoholic Fatty Liver ◽  
Induced Pluripotent ◽  
Liver Organoids ◽  
End Stage

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) affects 30–40% of adults and 10% of children in the US. About 20% of people with NAFLD develop non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis and liver cancer, and is projected to be a leading cause of liver transplantation in the near future. Human induced pluripotent stem cells (iPSC) from NASH patients are useful for generating a large number of hepatocytes for NASH modeling applications and identification of potential drug targets. We developed a novel defined in vitro differentiation process to generate cryopreservable hepatocytes using an iPSC panel of NASH donors and apparently healthy normal (AHN) controls. iPSC-derived hepatocytes displayed stage specific phenotypic markers, hepatocyte morphology, with bile canaliculi. Importantly, both fresh and cryopreserved definitive endoderm and hepatoblasts successfully differentiated to pure and functional hepatocytes with increased CYP3A4 activity in response to rifampicin and lipid accumulation upon fatty acid (FA) treatment. End-stage hepatocytes integrated into three-dimensional (3D) liver organoids and demonstrated increased levels of albumin secretion compared to aggregates consisting of hepatocytes alone. End-stage hepatocytes derived from NASH donors demonstrated spontaneous lipidosis without FA supplementation, recapitulating a feature of NASH hepatocytes in vivo. Cryopreserved hepatocytes generated by this protocol across multiple donors will provide a critical cell source to facilitate the fundamental understanding of NAFLD/NASH biology and potential high throughput screening applications for preclinical evaluation of therapeutic targets.

scholarly journals Leishmania donovani Parasites Are Inhibited by the Benzoxaborole AN2690 Targeting Leucyl-tRNA Synthetase

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Reetika Manhas ◽  
Smriti Tandon ◽  
Shib Sankar Sen ◽  
Neha Tiwari ◽  
Manoj Munde ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Drug Targets ◽  
Fungal Pathogens ◽  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Gene Replacement ◽  
Trna Synthetase ◽  
Content Type

ABSTRACT Visceral leishmaniasis is an important public health threat in parts of India. It is caused by a protozoan parasite, Leishmania donovani. Currently available drugs manifest severe side effects. Hence, there is a need to identify new drug targets and drugs. Aminoacyl-tRNA synthetases, required for protein synthesis, are known drug targets for bacterial and fungal pathogens. The aim of the present study was to obtain essentiality data for Leishmania donovani leucyl-tRNA synthetase (LdLRS) by gene replacement. Gene replacement studies indicate that this enzyme plays an essential role in the viability of this pathogenic organism and appears to be indispensable for its survival in vitro. The heterozygous mutant parasites demonstrated a growth deficit and reduced infectivity in mouse macrophages compared to the wild-type cells. We also report that Leishmania donovani recombinant LRS displayed aminoacylation activity and that the protein localized to both the cytosol and the mitochondrion. A broad-spectrum antifungal, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), was found to inhibit parasite growth in both the promastigote and amastigote stages in vitro as well as in vivo in BALB/c mice. This compound exhibited low toxicity to mammalian cells. AN2690 was effective in inhibiting the aminoacylation activity of the recombinant LdLRS. We provide preliminary chemical validation of LdLRS as a drug target by showing that AN2690 is an inhibitor both of L. donovani LRS and of L. donovani cell growth.

scholarly journals Identification of Common Molecular Signatures Shared between Alzheimer’s and Parkinson’s Diseases and Therapeutic Agents Exploration: An Integrated Genomics Approach

2021 ◽  
Author(s):  
Nairita Ahsan Faruqui ◽  
Durdana Hossain Prium ◽  
Sadrina Afrin Mowna ◽  
Tanjim Ishraq Rahaman ◽  
Arundhati Roy Dutta ◽  
...  
Keyword(s):  
Drug Targets ◽  
Interaction Analysis ◽  
Interaction Network ◽  
Therapeutic Agents ◽  
Molecular Signatures ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Effective Diagnosis

AbstractAlzheimer’s disease (AD) and Parkinson’s disease (PD) are two most prevalent age-related dementias that severely affect a large number of elderly people around the globe. Poor understanding of pathogenesis of these neurological diseases imposes challenge to discover therapeutic measures and effective diagnosis methods. In this study, a network-based approach was utilized to identify potential common molecular signatures and therapeutic agents for AD and PD. Protein-protein interaction analysis revealed NCK1, UBC, CDH1, CDC20, ACTB, PSMA7, PRPF8, RPL7, XRCC6 and HSP90AB1 as the best proteome signatures. Different regulatory transcriptional signatures i.e., YY1, NFKB1, BRCA1, TP53, GATA2, SREBF2, E2F1, FOXC1, RELA and NFIC and post-transcriptional signatures i.e., hsa-mir-186-5p, hsamir-92a-3p, hsa-mir-615-3p, hsa-let-7c-5p, hsa-mir-100-5p, hsa-mir-93-3p, hsa-mir-5681a, hsamir-484, hsa-mir-193b-3p and hsa-mir-16p-5p were identified from other interaction network. Drug-gene interaction study revealed possible therapeutic agents which may reverse the AD and PD condition. The scientific approach of this study should contribute to identify potential biomarkers, drug targets and therapeutic agents against AD and PD which should in turn advance the present efforts of scientists to secure effective diagnosis and therapeutic options. However, further in vivo and in vitro experiments might be required to validate the outcomes of this study.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli
Keyword(s):  
Drug Targets ◽  
Redox Homeostasis ◽  
Cost Effective ◽  
Structural Features ◽  
Mammalian Host ◽  
Neglected Diseases ◽  
Nitrogen Compounds ◽  
Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

scholarly journals In Vitro and In Vivo Antifungal Activity of Sorbicillinoids Produced by Trichoderma longibrachiatum

2021 ◽  
Vol 7 (6) ◽  
pp. 428
Author(s):  
Men Thi Ngo ◽  
Minh Van Nguyen ◽  
Jae Woo Han ◽  
Myung Soo Park ◽  
Hun Kim ◽  
...  
Keyword(s):  
Late Blight ◽  
Culture Filtrate ◽  
Fungal Pathogens ◽  
Gray Mold ◽  
Trichoderma Longibrachiatum ◽  
Chemical Structures ◽  
Natural Agents ◽  
Blight Disease

In the search for antifungal agents from marine resources, we recently found that the culture filtrate of Trichoderma longibrachiatum SFC100166 effectively suppressed the development of tomato gray mold, rice blast, and tomato late blight. The culture filtrate was then successively extracted with ethyl acetate and n-butanol to identify the fungicidal metabolites. Consequently, a new compound, spirosorbicillinol D (1), and a new natural compound, 2′,3′-dihydro-epoxysorbicillinol (2), together with 11 known compounds (3–13), were obtained from the solvent extracts. The chemical structures were determined by spectroscopic analyses and comparison with literature values. The results of the in vitro antifungal assay showed that of the tested fungal pathogens, Phytophthora infestans was the fungus most sensitive to the isolated compounds, with MIC values ranging from 6.3 to 400 µg/mL, except for trichotetronine (9) and trichodimerol (10). When tomato plants were treated with the representative compounds (4, 6, 7, and 11), bisvertinolone (6) strongly reduced the development of tomato late blight disease compared to the untreated control. Taken together, our results revealed that the culture filtrate of T. longibrachiatum SFC100166 and its metabolites could be useful sources for the development of new natural agents to control late blight caused by P. infestans.

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