scholarly journals What Can Electrochemical Methods Offer in Determining DNA–Drug Interactions?

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3478
Author(s):  
Sandra Ramotowska ◽  
Aleksandra Ciesielska ◽  
Mariusz Makowski
Keyword(s):  
Dna Sequences ◽  
Electrode Materials ◽  
High Reliability ◽  
Electrochemical Methods ◽  
Biologically Active ◽  
New Drugs ◽  
Binding Modes ◽  
Voltammetric Techniques ◽  
Experimental Approaches ◽  
Cellular Dna

The interactions of compounds with DNA have been studied since the recognition of the role of nucleic acid in organisms. The design of molecules which specifically interact with DNA sequences allows for the control of the gene expression. Determining the type and strength of such interaction is an indispensable element of pharmaceutical studies. Cognition of the therapeutic action mechanisms is particularly important for designing new drugs. Owing to their sensitivity, simplicity, and low costs, electrochemical methods are increasingly used for this type of research. Compared to other techniques, they require a small number of samples and are characterized by a high reliability. These methods can provide information about the type of interaction and the binding strength, as well as the damage caused by biologically active molecules targeting the cellular DNA. This review paper summarizes the various electrochemical approaches used for the study of the interactions between pharmaceuticals and DNA. The main focus is on the papers from the last decade, with particular attention on the voltammetric techniques. The most preferred experimental approaches, the electrode materials and the new methods of modification are presented. The data on the detection ranges, the binding modes and the binding constant values of pharmaceuticals are summarized. Both the importance of the presented research and the importance of future prospects are discussed.

Denaturing High Performance Liquid Chromatography and Bioinformatics - Two Modern Tools for Extracellular Superoxide Dismutase (SOD3) Gene Promoter Analysis

2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Corina Samoila ◽  
Alfa Xenia Lupea ◽  
Andrei Anghel ◽  
Marilena Motoc ◽  
Gabriela Otiman ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Transcription Factors ◽  
Liquid Chromatography ◽  
Dna Sequences ◽  
High Performance ◽  
Zinc Finger Protein ◽  
High Capacity ◽  
Gene Promoter ◽  
Experimental Approaches ◽  
Myeloid Zinc Finger

Denaturing High Performance Liquid Chromatography (DHPLC) is a relatively new method used for screening DNA sequences, characterized by high capacity to detect mutations/polymorphisms. This study is focused on the Transgenomic WAVETM DNA Fragment Analysis (based on DHPLC separation method) of a 485 bp fragment from human EC-SOD gene promoter in order to detect single nucleotide polymorphism (SNPs) associated with atherosclerosis and risk factors of cardiovascular disease. The fragment of interest was amplified by PCR reaction and analyzed by DHPLC in 100 healthy subjects and 70 patients characterized by atheroma. No different melting profiles were detected for the analyzed DNA samples. A combination of computational methods was used to predict putative transcription factors in the fragment of interest. Several putative transcription factors binding sites from the Ets-1 oncogene family: ETS member Elk-1, polyomavirus enhancer activator-3 (PEA3), protein C-Ets-1 (Ets-1), GABP: GA binding protein (GABP), Spi-1 and Spi-B/PU.1 related transcription factors, from the Krueppel-like family: Gut-enriched Krueppel-like factor (GKLF), Erythroid Krueppel-like factor (EKLF), Basic Krueppel-like factor (BKLF), GC box and myeloid zinc finger protein MZF-1 were identified in the evolutionary conserved regions. The bioinformatics results need to be investigated further in others studies by experimental approaches.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

Integration of viral DNA sequences in cells transformed by adenovirus 2 or SV40

1980 ◽  
Vol 210 (1180) ◽  
pp. 423-435 ◽  
Keyword(s):  
Cell Lines ◽  
Dna Sequences ◽  
Viral Genome ◽  
Viral Dna ◽  
Viral Genomes ◽  
Viral Dnas ◽  
Cellular Dna ◽  
Viral Insertion ◽  
Viral Sequences ◽  
Heteroduplex Formation

We have cloned and propagated in prokaryotic vectors the viral DNA sequences that are integrated in a variety of cells transformed by adenovirus 2 or SV40. Analysis of the clones reveals that the viral DNA sequences sometimes are arranged in a simple fashion, collinear with the viral genome; in other cell lines there are complex arrangements of viral sequences in which tracts of the viral genome are inverted with respect to each other. In several cases the nucleotide sequences at the joints between cell and viral sequences have been determined: usually there is a sharp transition between cellular and viral DNAs. The viral sequences are integrated at different locations within the genomes of different cell lines; likewise there is no specific site on the viral genomes at which integration occurs. Sometimes the viral sequences are integrated within repetitive cellular DNA, and sometimes within unique sequences. In some cases there is evidence that the viral sequences along with the flanking cell DNA have been amplified after integration. The sequences that flank the viral insertion in the line of SV40-transformed rat cells known as 14B have been used as probes to isolate, from untransformed rat cells, clones that carry the region of the chromosome in which integration occurred. Analysis of the structure of these clones by restriction endonuclease digestion and heteroduplex formation shows that a rearrangement of cellular sequences has occurred, presumably as a consequence of integration.

Catalytic properties of plate-like cadmium oxide nanoparticles in removal of sulfathiazole with anticancer activity

2018 ◽  
Vol 41 (3-4) ◽  
pp. 121-128 ◽  
Author(s):  
Leila Hoseini ◽  
Azar Bagheri
Keyword(s):  
Binding Constant ◽  
Cadmium Oxide ◽  
Reaction Times ◽  
Dna Interaction ◽  
New Drugs ◽  
Binding Modes ◽  
Hyperchromic Effect ◽  
Initial Ph ◽  
Ft Ir ◽  
Spectroscopy Studies

Abstract The study of the interaction of drugs with DNA is very exciting and significant not only for understanding the mechanism of the interaction but also for the design of new drugs. Here, we report the results of Fourier transform infrared (FT-IR) and ultraviolet (UV)-visible spectroscopy studies to determine the external binding modes of sulfathiazole (STZ), and the binding constant and stability of the STZ-DNA complex in aqueous solution. The results of absorption spectra showed that the interaction of STZ-DNA is weak because there is only a hyperchromic effect. A hyperchromic effect reflects the corresponding changes of DNA in its conformation and structure after the drug-DNA interaction has occurred. Spectroscopic evidence revealed that STZ binds DNA with an overall binding constant of K (STZ-DNA)=0.42×103 m−1. FT-IR spectroscopy showed that the complexation of STZ with DNA occurred via A-T and PO2 groups. Nano cadmium hydroxide has been synthesized using hexamine as the template at room temperature. Then, this nano cadmium hydroxide recrystallizes into nano cadmium oxide (CdO) at 400°C for 2 h. The product was characterized by using X-ray diffraction and scanning electron microscopy. The presence of drugs in aquatic media has emerged in the last decade as a new environmental risk. The other aim of this study was to investigate the degradation of the STZ antibiotic by nanosized CdO under ultraviolet irradiation. Various experimental parameters, such as initial CdO concentration, initial pH, and reaction times, were investigated. According to the results, this method has a good performance in the removal of STZ.

Oncogenes in Laryngeal Cancer: Serial Passage of Transformed Cellular DNA

1985 ◽  
Vol 93 (3) ◽  
pp. 346-350 ◽  
Author(s):  
William H. Friedman ◽  
Barry N. Rosenblum ◽  
Paul Loewenstein ◽  
Helen Thornton ◽  
George Katsantonis ◽  
...  
Keyword(s):  
Laryngeal Cancer ◽  
Dna Sequences ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Serial Passage ◽  
3T3 Cells ◽  
Human Dna ◽  
Cellular Dna ◽  
Nih 3T3 ◽  
Narrow Bands

DNA originally extracted from squamous cell cancer of the larynx has been serially passaged through transformed populations of NIH/3T3 mouse fibroblasts. The transformed foci were then harvested, cloned to volume, and incubated with a fresh population of NIH/3T3 cells in a second passage. Transforming efficiencies were enhanced by serial passage. In addition, Southern Blot analysis of the transformed foci revealed hybridization between transformant DNA and human probe DNA from the Alu family of conserved human DNA sequences. In the first passage this hybridization took the form of diffuse homology throughout the entire molecular weight distribution. The second-passage DNA showed “narrow bands” indicating the possibility that an oncogene has been identified in laryngeal cancer and that serial passage has eliminated contaminating human sequences. Repetitive transfection in third- and fourth-passage studies is now being completed.

scholarly journals Natural Compound Modulates the Cervical Cancer Microenvironment—A Pharmacophore Guided Molecular Modelling Approaches

2018 ◽  
Vol 7 (12) ◽  
pp. 551 ◽  
Author(s):  
Shailima Rampogu ◽  
Doneti Ravinder ◽  
Smita Pawar ◽  
Keun Lee
Keyword(s):  
Cervical Cancer ◽  
Md Simulations ◽  
Data Bank ◽  
Docking Studies ◽  
New Drugs ◽  
Binding Modes ◽  
Cervical Cancer Cells ◽  
Causative Agents ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

Cervical cancer is regarded as one of the major burdens noticed in women next to breast cancer. Although, human papilloma viruses (HPVs) are regarded as the principal causative agents, they require certain other factors such as oestrogen hormone to induce cervical cancer. Aromatase is an enzyme that converts androgens into oestrogens and hindering this enzyme could subsequently hamper the formation of oestrogen thereby alleviating the disease. Accordingly, in the current investigation, a structure based pharmacophore was generated considering two proteins bearing the Protein Data Bank (PDB) codes 3EQM (pharm 1) and 3S7S (pharm 2), respectively. The two models were employed as the 3D query to screen the in-house built natural compounds database. The obtained 51 compounds were escalated to molecular docking studies to decipher on the binding affinities and to predict the quintessential binding modes which were affirmed by molecular dynamics (MD) simulations. The compound has induced dose-dependent down regulation of PP2B, Nitric oxide synthase-2 (NOS2), and Interleukin 6 (IL-6) genes in the HeLa cells and has modulated the expression of apoptotic genes such as Bax, Bcl2, and caspases-3 at different concentrations. These results guide us to comprehend that the identified aromatase inhibitor was effective against the cervical cancer cells and additionally could server as scaffolds in designing new drugs.

scholarly journals Betanin: a promising molecule for biomedical applications

2020 ◽  
Vol 10 (3) ◽  
pp. 5392-5399
Keyword(s):  
Positive Impact ◽  
Pharmaceutical Products ◽  
Free Radical Scavenger ◽  
Biologically Active ◽  
New Drugs ◽  
Radical Scavenger ◽  
Therapeutic Effects ◽  
Pharmacological Properties ◽  
Natural Colorant ◽  
Anti Oxidant

Plants with medicinal properties possess beneficial influences on health and disease. Different plant parts and extracts carry valuable active ingredients with pharmacological properties that lead to developing new drugs. Terminalia bellirica is among those plants that have been formulated as pharmaceutical products. This is attributed to its biologically active phenolics and tannins exhibiting analgesic, anti-hypertensive, anti-microbial, anti-diabetic, anti-oxidant, as well as, other pharmacological properties. Beetroot has been shown to be rich in nitrates with a positive impact on the cardiovascular system. Beetroot contains a number of useful ingredients as the free-radical scavenger ascorbic acid, the anti-inflammatory flavonoids and the anti-oxidant carotenoids. Moreover, beetroot is rich in the natural colorant betalains that are further classified into betacyanins and betaxanthins. Betanin, is one of the major constituents of beetroots that have been postulated to possess significant beneficial therapeutic effects in a number of conditions and diseases. However, several studies have demonstrated the relatively poor bioavailability of betanin upon oral administration. In the current review we aim to highlight some of the latest researches dealing with the therapeutic properties of betanin in different disease conditions, the possible mechanistic pathways beyond such beneficial effects and plausible strategies capable of enhancing its stability and bioavailability.

Strategies for analysis of gene expression: pulmonary surfactant proteins

1990 ◽  
Vol 259 (4) ◽  
pp. L185-L197
Author(s):  
B. R. Stripp ◽  
J. A. Whitsett ◽  
D. L. Lattier
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Pulmonary Surfactant ◽  
Transcriptional Control ◽  
Lung Surfactant ◽  
Surfactant Protein ◽  
Biologically Active ◽  
Surfactant Proteins ◽  
Regulatory Sequences ◽  
Control Mechanisms

Gene transcription is regulated by the formation of protein-DNA complexes that influence the rate of specific initiation of transcription by RNA polymerase. Recent experimental advances allowing the identification of cis regulatory sequences that specify the binding of trans acting protein factors have made significant contributions to our understanding of the mechanistic complexities of transcriptional regulation. These methodologies have prompted the use of similar strategies to elucidate transcriptional control mechanisms involved in the tissue specific and developmental regulation of pulmonary surfactant protein gene expression. The purpose of this review is to describe various methodologies by which molecular biologists identify and subsequently assay regions of nucleic acids presumed to be integral in gene regulation at the level of transcription. It is well established that genes encoding surfactant proteins are subject to regulation by hormones, cytokines, and a variety of biologically active reagents. Perhaps future studies utilizing molecular tools outlined in this review will be valuable in identification of DNA sequences and protein factors required for the regulation of lung surfactant genes.

Look Closely, the Beautiful May Be Small: Precursor-Derived Peptides in Plants

2019 ◽  
Vol 70 (1) ◽  
pp. 153-186 ◽  
Author(s):  
Vilde Olsson ◽  
Lisa Joos ◽  
Shanshuo Zhu ◽  
Kris Gevaert ◽  
Melinka A. Butenko ◽  
...  
Keyword(s):  
Cell Communication ◽  
Peptide Ligands ◽  
Biologically Active ◽  
Peptide Ligand ◽  
Long Distance ◽  
Signaling Systems ◽  
Experimental Approaches ◽  
Biologically Active Peptide ◽  
Subsequent Activation ◽  
Complex Signaling

During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here, we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs. We discuss different experimental approaches that can be used to match peptide ligands with their receptors. Lastly, we explore how peptides evolved from basic signaling units regulating essential processes in plants to more complex signaling systems as new adaptive traits developed and how nonplant organisms exploit this signaling machinery by producing peptide mimics.

scholarly journals Ascomycete Aspergillus oryzae Is an Efficient Expression Host for Production of Basidiomycete Terpenes by Using Genomic DNA Sequences

2019 ◽  
Vol 85 (15) ◽  
Author(s):  
Shota Nagamine ◽  
Chengwei Liu ◽  
Jumpei Nishishita ◽  
Takuto Kozaki ◽  
Kaho Sogahata ◽  
...  
Keyword(s):  
Natural Products ◽  
Aspergillus Oryzae ◽  
Dna Sequences ◽  
Genomic Dna ◽  
Genome Mining ◽  
Biologically Active ◽  
Biosynthetic Genes ◽  
Content Type ◽  
Content System ◽  
Basidiomycete Fungi

ABSTRACT Basidiomycete fungi are an attractive resource for biologically active natural products for use in pharmaceutically relevant compounds. Recently, genome projects on mushroom fungi have provided a great deal of biosynthetic gene cluster information. However, functional analyses of the gene clusters for natural products were largely unexplored because of the difficulty of cDNA preparation and lack of gene manipulation tools for basidiomycete fungi. To develop a versatile host for basidiomycete genes, we examined gene expression using genomic DNA sequences in the robust ascomycete host Aspergillus oryzae, which is frequently used for the production of metabolites from filamentous fungi. Exhaustive expression of 30 terpene synthase genes from the basidiomycetes Clitopilus pseudo-pinsitus and Stereum hirsutum showed two splicing patterns, i.e., completely spliced cDNAs giving terpenes (15 cases) and mostly spliced cDNAs, indicating that A. oryzae correctly spliced most introns at the predicted positions and lengths. The mostly spliced cDNAs were expressed after PCR-based removal of introns, resulting in the successful production of terpenes (14 cases). During this study, we observed relatively frequent mispredictions in the automated program. Hence, the complementary use of A. oryzae expression and automated prediction will be a powerful tool for genome mining. IMPORTANCE The recent large influx of genome sequences from basidiomycetes, which are prolific producers of bioactive natural products, may provide opportunities to develop novel drug candidates. The development of a reliable expression system is essential for the genome mining of natural products because of the lack of a tractable host for heterologous expression of basidiomycete genes. For this purpose, we applied the ascomycete Aspergillus oryzae system for the direct expression of fungal natural product biosynthetic genes from genomic DNA. Using this system, 29 sesquiterpene synthase genes and diterpene biosynthetic genes for bioactive pleuromutilin were successfully expressed. Together with the use of computational tools for intron prediction, this Aspergillus oryzae system represents a practical method for the production of basidiomycete natural products.

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