scholarly journals Nonclassical Biological Activities of Quinolone Derivatives

2011 ◽  
Vol 15 (1) ◽  
pp. 52 ◽  
Author(s):  
Mohsen Daneshtalab ◽  
Abeer Ahmed
Keyword(s):  
Mammalian Cells ◽  
Antibacterial Agents ◽  
Biological Activities ◽  
Antiviral Agent ◽  
Bioactive Molecules ◽  
Structural Modifications ◽  
Further Development ◽  
Derivatives Of ◽  
Ns5b Polymerase

Quinolones are considered as a big family of multi-faceted drugs; their chemical synthesis is flexible and can be easily adapted to prepare new congeners with rationally devised structures. This is shown by the description of many thousands of derivatives in the literature. Scientists could accurately describe their QSAR, which is essential for effective drug design. This also gave them the chance to discover new and unprecedented activities, which makes quinolones an endless source of hope and enables further development of new clinically useful drugs. Quinolones are among the most common frameworks present in the bioactive molecules that have dominated the market for more than four decades. Since 1962, 4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial agents. Quinolones have a broad and potent spectrum of activity and are also used as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been reported to display “nonclassical” biological activities, such as antitumor, anti-HIV-1 integrase, anti- HCV-NS3 helicase and -NS5B-polymerase activities. The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent and/or an antiviral agent. Indeed, quinolones’ antimicrobial action is distinguishable among antibacterial agents, because they target different type II topoisomerase enzymes. Many derivatives of this family show high activity against bacterial topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured mammalian cells and in vivo tumor models. Moreover, quinolones have shown antiviral activity against HIV and HCV viruses. In this context the quinolones family of drugs seem to link three different biological activities (antibacterial, anticancer, and the antiviral profiles) and the review will also provide an insight into the different mechanisms responsible for these activities among different species. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5995
Author(s):  
Hallysson Douglas Andrade de Araújo ◽  
Hianna Arely Milca Fagundes Silva ◽  
José Guedes da Silva Júnior ◽  
Mônica Camelo Pessoa de Azevedo Albuquerque ◽  
Luana Cassandra Breitenbach Barroso Coelho ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Characteristics ◽  
Usnic Acid ◽  
Raw Material ◽  
Structural Modifications ◽  
Hydrophobic Molecule ◽  
Antiparasitic Agents ◽  
Toxic Molecule

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.

scholarly journals Secondary Metabolites from Gorgonian Corals of the Genus Eunicella: Structural Characterizations, Biological Activities, and Synthetic Approaches

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 129
Author(s):  
Dario Matulja ◽  
Maria Kolympadi Markovic ◽  
Gabriela Ambrožić ◽  
Sylvain Laclef ◽  
Sandra Kraljević Pavelić ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Antimicrobial Activities ◽  
Chemical Structures ◽  
Gorgonian Corals ◽  
Synthetic Approaches ◽  
Further Development

Gorgonian corals, which belong to the genus Eunicella, are known as natural sources of diverse compounds with unique structural characteristics and interesting bioactivities both in vitro and in vivo. This review is focused primarily on the secondary metabolites isolated from various Eunicella species. The chemical structures of 64 compounds were divided into three main groups and comprehensively presented: a) terpenoids, b) sterols, and c) alkaloids and nucleosides. The observed biological activities of depicted metabolites with an impact on cytotoxic, anti-inflammatory, and antimicrobial activities were reviewed. The most promising biological activities of certain metabolites point to potential candidates for further development in pharmaceutical, cosmetic, and other industries, and are highlighted. Total synthesis or the synthetic approaches towards the desired skeletons or natural products are also summarized.

scholarly journals Regulation of c-Fes Tyrosine Kinase and Biological Activities by N-Terminal Coiled-Coil Oligomerization Domains

1999 ◽  
Vol 19 (12) ◽  
pp. 8335-8343 ◽  
Author(s):  
Haiyun Cheng ◽  
Jim A. Rogers ◽  
Nancy A. Dunham ◽  
Thomas E. Smithgall
Keyword(s):  
Tyrosine Kinase ◽  
Mammalian Cells ◽  
Protein Tyrosine Kinase ◽  
Biological Activities ◽  
Coiled Coil ◽  
Protein Tyrosine ◽  
Coiled Coil Domain ◽  
Fibroblast Transformation

ABSTRACT The cytoplasmic protein-tyrosine kinase Fes has been implicated in cytokine signal transduction, hematopoiesis, and embryonic development. Previous work from our laboratory has shown that active Fes exists as a large oligomeric complex in vitro. However, when Fes is expressed in mammalian cells, its kinase activity is tightly repressed. The Fes unique N-terminal sequence has two regions with strong homology to coiled-coil-forming domains often found in oligomeric proteins. Here we show that disruption or deletion of the first coiled-coil domain upregulates Fes tyrosine kinase and transforming activities in Rat-2 fibroblasts and enhances Fes differentiation-inducing activity in myeloid leukemia cells. Conversely, expression of a Fes truncation mutant consisting only of the unique N-terminal domain interfered with Rat-2 fibroblast transformation by an activated Fes mutant, suggesting that oligomerization is essential for Fes activation in vivo. Coexpression with the Fes N-terminal region did not affect the transforming activity of v-Src in Rat-2 cells, arguing against a nonspecific suppressive effect. Taken together, these findings suggest a model in which Fes activation may involve coiled-coil-mediated interconversion of monomeric and oligomeric forms of the kinase. Mutation of the first coiled-coil domain may activate Fes by disturbing intramolecular coiled-coil interaction, allowing for oligomerization via the second coiled-coil domain. Deletion of the second coiled-coil domain blocks fibroblast transformation by an activated form of c-Fes, consistent with this model. These results provide the first evidence for regulation of a nonreceptor protein-tyrosine kinase by coiled-coil domains.

scholarly journals Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages

2018 ◽  
Author(s):  
Talha Bin Emran ◽  
Mitsuhiro Iyori ◽  
Yuki Ono ◽  
Fitri Amelia ◽  
Yenni Yusuf ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Independent Manner ◽  
Liver Stage ◽  
Interferon Stimulated Genes ◽  
Rna Transcripts ◽  
Double Stranded Dna ◽  
Further Development

ABSTRACTBaculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequent Plasmodium berghei sporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN-α and IFN-γ were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. The in vivo passive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.

scholarly journals Building a Foundation for Precision Onco-Nutrition: Docosahexaenoic Acid and Breast Cancer

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 157
Author(s):  
Henry J. Thompson ◽  
Elizabeth S. Neil ◽  
John N. McGinley ◽  
Vanessa K. Fitzgerald ◽  
Karam El Bayoumy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Docosahexaenoic Acid ◽  
Anticancer Activity ◽  
Mammalian Cells ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Biological Activities ◽  
Treatment Strategies ◽  
Cell Number

In vivo evidence of heterogeneous effects of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of breast cancer has been reported and is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of the disease. Similarly, available evidence indicates that many metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite-specific biological activities. To begin to unravel the complex relationships among molecular subtypes and effects exerted by specific N3FA metabolites on those pathways, proof-of-concept experiments were conducted using cell lines representative of common molecular subtypes of human breast cancer. N3FA differed in anticancer activity with docosahexaenoic acid (DHA) having greater anticancer activity than eicosapentaenoic acid. 4-oxo-docosahexaenoic (4-oxo-DHA), a penultimate metabolite of 5-lipoxygenase mediated DHA metabolism, induced dose-dependent inhibition of cell number accumulation with apoptosis as a primary effector mechanism. Interrogation of protein expression data using the Ingenuity Pathway Analysis (IPA) bioinformatics platform indicated that 4-oxo-DHA differentially impacted six canonical pathways and the cellular functions they regulate across common molecular subtypes of breast cancer. This included the endocannabinoid pathway for cancer inhibition that has not been previously reported. These findings provide a rationale for juxtaposing molecular subtype targeted treatment strategies with the adjuvant use of specific N3FA metabolites as an example of precision onco-nutrition (PON) for the management and control of breast cancer.

scholarly journals Protein Hydrolysates from Anchovy (Engraulis encrasicolus) Waste: In Vitro and In Vivo Biological Activities

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 86 ◽  
Author(s):  
Alessia Giannetto ◽  
Emanuela Esposito ◽  
Marika Lanza ◽  
Sabrina Oliva ◽  
Kristian Riolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biological Activities ◽  
Protein Hydrolysates ◽  
Bioactive Molecules ◽  
Nutritional Properties ◽  
Fish Waste ◽  
In Vivo Models ◽  
Engraulis Encrasicolus

Fish waste utilization to obtain protein hydrolysates has been demonstrated to be a useful strategy to face both environmental and economic impacts while obtaining high-value products with remarkable biological and nutritional properties. In the present study, protein hydrolysates obtained from anchovy Engraulis encrasicolus (APH) by-products were assessed for their potential biological activities in both in vitro and in vivo models. The treatment with APH exerted a significant protection against LPS-induced inflammation in RAW 264.7 cells, decreasing the protein expression of pro-inflammatory mediators (i.e., COX-2) and inhibiting the nuclear translocation of NF-κB through IκB-α. Moreover, APH modulated the expression of iNOS, MnSOD and HO-1, thus decreasing the severity of oxidative stress. The supplementation of APH in the diet of ApoE knockout mice down-regulated the proinflammatory cytokines (i.e., TNF-α, IL-1α, IL-1β, IL-6) in both aorta and heart tissues, and modulated the expression of oxidative stress-related genes (Cu/ZnSod, MnSod, Cat, Gpx and Ho), indicating that APH can exert a beneficial role, having anti-inflammatory and antioxidant activities. The nutritional properties of APH, together with their biological activities herein reported, highlight the possibility of obtaining bioactive molecules from fish waste and encourage their use as potential nutraceuticals in food and pharmaceutical industries in the next future.

scholarly journals New Insights into the Bacterial RNA Polymerase Inhibitor CBR703 as a Starting Point for Optimization as an Anti-Infective Agent

2014 ◽  
Vol 58 (7) ◽  
pp. 4242-4245 ◽  
Author(s):  
Weixing Zhu ◽  
Jörg Haupenthal ◽  
Matthias Groh ◽  
Michelle Fountain ◽  
Rolf W. Hartmann
Keyword(s):  
Rna Polymerase ◽  
Biofilm Formation ◽  
Mammalian Cells ◽  
Antibacterial Agents ◽  
Antibacterial Activities ◽  
Bacterial Rna ◽  
Starting Point ◽  
Polymerase Inhibitor ◽  
Derivatives Of ◽  
Infective Agent

ABSTRACTCBR703 was reported to inhibit bacterial RNA polymerase (RNAP) and biofilm formation, considering it to be a good candidate for further optimization. While synthesized derivatives of CBR703 did not result in more-active RNAP inhibitors, we observed promising antibacterial activities. These again correlated with a significant cytotoxicity toward mammalian cells. Furthermore, we suspect the promising effects on biofilm formation to be artifacts. Consequently, this class of compounds can be considered unattractive as antibacterial agents.

scholarly journals Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4960
Author(s):  
Olalla Barreiro-Costa ◽  
Gabriela Morales-Noboa ◽  
Patricio Rojas-Silva ◽  
Eliana Lara-Barba ◽  
Javier Santamaría-Aguirre ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
In Silico ◽  
Potential Application ◽  
Mammalian Cells ◽  
Biological Activities ◽  
Antioxidant Properties ◽  
Therapeutic Use ◽  
Derivatives Of

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

scholarly journals Curcumins and its derivatives as potential inhibitors of New Coronavirus (COVID-19) main protease: an in silico strategy

2022 ◽  
Vol 11 (1) ◽  
pp. e6511124334
Author(s):  
Daniela Ribeiro Alves ◽  
Matheus Nunes da Rocha ◽  
Camila Caldas Oliveira Passos ◽  
Márcia Machado Marinho ◽  
Emmanuel Silva Marinho ◽  
...  
Keyword(s):  
Biological Activities ◽  
Specific Treatment ◽  
Bioactive Molecules ◽  
Curcumin Derivatives ◽  
Main Protease ◽  
Protein Receptors ◽  
Future Evaluation ◽  
Potential Inhibitors

Coronavirus (COVID-19) disease outbreak caused a worldwide pandemic with a powerful lethal potential and still, there is no specific treatment to it. Natural bioactive molecules like curcumins were investigated in this work aiming to block the active site of COVID-19 Main protease (Mpro), since they present several biological activities, being more suitable in terms of fewer side effects, once this disease overloads the immune system of patients. Hereby, curcumin and several derivatives were screened for their ability to react with Mpro receptors (PDB: 6LU7). N3, Azithromycin (AZT), and Baracitinib (BRT) were evaluated as positive controls and in combined therapeutics possibilities with curcumins. N3, AZT, and BRT bound to different protein receptors, and also it was observed that N3 bound in the same site as hexahydrocurcumin and curcumin glucuronide bound at the AZT’s site and bisdemethoxycurcumin, curcumin, curcumin sulfate, cyclocurcumin, demethoxycurcumin, dihydrocurcumin and hexahydrocurcuminol bound at BRT’s site. All molecules analyzed have high force interaction fields. Once the viral activity is mainly intracellular, these compounds also were evaluated for their hydropathic abilities. All molecules were classified and considered capable of membrane cell invading. These results suggest that the therapeutic approach of the curcumin derivatives associated with AZT and the antiviral inhibitor N3 is promissory for future evaluation of their synergism in in vitro and in vivo tests to define their additional viability in the treatment of COVID-19.

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