scholarly journals Synthesis and Anticancer Activity of CDDO and CDDO-Me, Two Derivatives of Natural Triterpenoids

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4097 ◽  
Author(s):  
Rebecca Borella ◽  
Luca Forti ◽  
Lara Gibellini ◽  
Anna De Gaetano ◽  
Sara De Biasi ◽  
...  
Keyword(s):  
Biological Effects ◽  
Chemical Properties ◽  
Cell Types ◽  
Telomerase Activity ◽  
Culture Cell ◽  
Protease Inhibition ◽  
Mitochondrial Functions ◽  
Anti Inflammatory ◽  
Apoptotic Pathways ◽  
Derivatives Of

Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me.

scholarly journals Prenylated Flavonoids fromMorus albaL. Cause Inhibition of G1/S Transition in THP-1 Human Leukemia Cells and Prevent the Lipopolysaccharide-Induced Inflammatory Response

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Peter Kollar ◽  
Tomáš Bárta ◽  
Jan Hošek ◽  
Karel Souček ◽  
Veronika Müller Závalová ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Inflammatory Response ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
Biological Effects ◽  
Cell Types ◽  
Human Leukemia ◽  
Cycle Progression ◽  
Prenylated Flavonoids ◽  
Anti Inflammatory

Morus albaL. (MA) is a natural source of many compounds with different biological effects. It has been described to possess anti-inflammatory, antioxidant, and hepatoprotective activities. The aim of this study was to evaluate cytotoxicity of three flavonoids isolated from MA (kuwanon E, cudraflavone B, and4′-O-methylkuwanon E) and to determine their effects on proliferation of THP-1 cells, and on cell cycle progression of cancer cells. Anti-inflammatory effects were also determined for all three given flavonoids. Methods used in the study included quantification of cells by hemocytometer and WST-1 assays, flow cytometry, western blotting, ELISA, and zymography. From the three compounds tested, cudraflavone B showed the strongest effects on cell cycle progression and viability of tumor and/or immortalized cells and also on inflammatory response of macrophage-like cells. Kuwanon E and4′-O-methylkuwanon E exerted more sophisticated rather than direct toxic effect on used cell types. Our data indicate that mechanisms different from stress-related or apoptotic signaling pathways are involved in the action of these compounds. Although further studies are required to precisely define the mechanisms of MA flavonoid action in human cancer and macrophage-like cells, here we demonstrate their effects combining antiproliferative and anti-inflammatory activities, respectively.

scholarly journals Studying of analgesic and anti-inflammatory activity of 2,4-dioxobutanoic acid hydrazine derivatives

2020 ◽  
Vol 37 (4) ◽  
pp. 115-119
Author(s):  
Natalia A. Pulina ◽  
Aleksander S. Kuznecov ◽  
Svetlana V. Chashchina
Keyword(s):  
Biological Activities ◽  
Biological Effects ◽  
Water Soluble ◽  
Inflammatory Activity ◽  
Synthesis Methods ◽  
Hot Plate Test ◽  
Hydrazine Derivatives ◽  
Anti Inflammatory ◽  
The Relationship ◽  
Derivatives Of

Objective. To study the analgesic and anti-inflammatory activity of water-soluble hydrazine derivatives of 2,4-dioxobutanoic acids, as well as to determine the relationship between the structure of substances and their biological effects. Materials and methods. The laboratory synthesis methods were applied to obtain 2-hydrazine derivatives of 2,4-dioxobutanoic acids. The compounds were tested for biological activity using a hot plate test in mice and an acute inflammatory reaction caused by carrageenan-induced paw edema in rats. Results. The analgesic activity of four compounds is comparable to that of nimesulide. One of the substances obtained is found to exhibit higher anti-inflammatory activity than nimesulide during the 1st and 3rd hours of the experiment. Two compounds with a combination of high analgesic and anti-inflammatory activity were identified. The effect of certain radicals in the structure of the substances on the activities studied was discovered. Conclusions. The revealed relationship between the structure of original compounds and their biological activities can be used in the further synthesis and search for new domestic pharmaceutical substances with investigated effects.

scholarly journals Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2908
Author(s):  
Samanta Mecocci ◽  
Federica Gevi ◽  
Daniele Pietrucci ◽  
Luca Cavinato ◽  
Francesco R. Luly ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Metabolic Pathways ◽  
Biological Fluid ◽  
Biological Effects ◽  
Goat Milk ◽  
Cell Types ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Almost All

In recent years, extracellular vesicles (EVs), cell-derived micro and nano-sized structures enclosed in a double-layer membrane, have been in the spotlight for their high potential in diagnostic and therapeutic applications. Indeed, they act as signal mediators between cells and/or tissues through different mechanisms involving their complex cargo and exert a number of biological effects depending upon EVs subtype and cell source. Being produced by almost all cell types, they are found in every biological fluid including milk. Milk EVs (MEVs) can enter the intestinal cells by endocytosis and protect their labile cargos against harsh conditions in the intestinal tract. In this study, we performed a metabolomic analysis of MEVs, from three different species (i.e., bovine, goat and donkey) by mass spectroscopy (MS) coupled with Ultrahigh-performance liquid chromatography (UHPLC). Metabolites, both common or specific of a species, were identified and enriched metabolic pathways were investigated, with the final aim to evaluate their anti-inflammatory and immunomodulatory properties in view of prospective applications as a nutraceutical in inflammatory conditions. In particular, metabolites transported by MEVs are involved in common pathways among the three species. These metabolites, such as arginine, asparagine, glutathione and lysine, show immunomodulating effects. Moreover, MEVs in goat milk showed a greater number of enriched metabolic pathways as compared to the other kinds of milk.

ID: 51: CHEMOTHERAPEUTIC POTENTIAL OF LIPOXINS IN KAPOSI'S SARCOMA AND PRIMARY EFFUSION LYMPHOMA

2016 ◽  
Vol 64 (4) ◽  
pp. 954.3-955
Author(s):  
XM Huang ◽  
AC Hwang ◽  
N Sharma-Walia
Keyword(s):  
Kaposi's Sarcoma ◽  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
B Cell Lymphoma ◽  
Cell Types ◽  
Body Cavity ◽  
Anti Inflammatory ◽  
Apoptotic Pathways

Current treatments for Kaposi's Sarcoma (KS) and Primary Effusion Lymphoma (PEL) rely on systemic chemotherapeutics developed for non-virus-associated cancers that target DNA replication of all dividing cells. Other treatment methods aim at keeping immune system healthy and infection under control through surgery. All of the above approaches have low efficacy, high cost, and high risk of secondary malignancies especially in immuno-compromised patients. Hence, there is an emerging need to look for alternative treatment focused on KS or PEL host molecules, such as Lipoxins. Lipoxins are anti-inflammatory molecules that can target a variety of pro-inflammatory pathways of KS and PEL. Previous results from our lab have shown that level of ALX receptor (ALXR) does not change after Kaposi's Sarcoma Herpes Virus (KSHV) infection, leading to the potential use of Lipoxins to trigger anti-inflammatory and pro-apoptotic pathways as treatment of KS and PEL.In this study, we investigated downstream signaling in KSHV harboring body cavity B cell lymphoma (BCBL-1) cells induced by Lipoxin treatment to assess its pro-apoptotic effect. We treated 5–10×106 BCBL-1 cells with solvent control (EtOH), Lipoxin (100 mM), or Epilipoxin (100 mM) for 48 and 72 hrs. Downstream phosphorylation of Akt, NF-kB p65, and ERK were assessed using Western blotting and pro-apoptotic gene changes were detected using Real-Time PCR. Cell survival and cell cycle progression was assessed using BrdU FACS analysis. We found that Lipoxin and Epilipoxin treatment downregulated NF-kB and ERK activation via ALXR binding while Akt signaling was not affected. We also found that Lipoxin successfully upregulated pro-apoptotic genes such as BIM-1, BAX, BCL-10, and p53 compared to control. Lipoxin treatment also led to decreased S-phase progression and induction of apoptosis. In conclusion, our study suggests that Lipoxins have therapeutic potential for PEL and should be explored in KS and other PEL cell types.

Ultrastructural Changes in Three Different Mammalian Cells Following Ultraviolet Laser Irradiation

1972 ◽  
Vol 30 ◽  
pp. 350-351
Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki
Keyword(s):  
Ultraviolet Light ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Survival Rates ◽  
Chinese Hamster ◽  
Cell Types ◽  
Differential Sensitivity ◽  
Ultrastructural Changes ◽  
Ultraviolet Laser

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.

Isatin: A Scaffold with Innumerable Biodiversity

2020 ◽  
Vol 20 ◽  
Author(s):  
Priyobrata Nath ◽  
Agnish Mukherjee ◽  
Sougata Mukherjee ◽  
Sabyasachi Banerjee ◽  
Samarpita Das ◽  
...  
Keyword(s):  
Biological Effects ◽  
Scientific Information ◽  
Research Work ◽  
Chemical Properties ◽  
Industrial Applications ◽  
Biologically Relevant ◽  
Extensive Information ◽  
Relevant Compound ◽  
A Minor ◽  
Clinical Conditions

: Isatin is an endogenous and a significant category of fused heterocyclic component, widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains indole nucleus having both lactam and keto moiety which while being a part of a molecular framework exerted several biological effects, viz.; antimicrobial, antitubercular, anticonvulsant, anticancer etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged to be a drug. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure Activity Relationships study thus developed through a gamut of scientific information indicates the importance of mostly electron withdrawing groups, halogens, nitro, alkoxy and to a minor extent groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at position 2 and 3 sometimes become insignificant as fusion with a heterocycle at those position resulted in a biologically relevant compound.

scholarly journals Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 957
Author(s):  
Mamona Nazir ◽  
Muhammad Saleem ◽  
Muhammad Imran Tousif ◽  
Muhammad Aijaz Anwar ◽  
Frank Surup ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Biological Effects ◽  
Structural Diversity ◽  
Chemical Diversity ◽  
Biosynthetic Pathways ◽  
Natural Sources ◽  
Hybrid Compounds ◽  
Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

scholarly journals New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Visceral Pain ◽  
Biological Effects ◽  
Maximum Effect ◽  
Tail Flick ◽  
Paw Edema ◽  
Cell Viability Assay ◽  
Thermal Nociception ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

scholarly journals Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  
Keyword(s):  
Bile Acids ◽  
Biological Effects ◽  
Cellular Respiration ◽  
Full Potential ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Wide Range ◽  
Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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