Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

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Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

Pharmaceuticals ◽

10.3390/ph13120463 ◽

2020 ◽

Vol 13 (12) ◽

pp. 463

Author(s):

Diana Xochiquetzal Robledo-Cadena ◽

Juan Carlos Gallardo-Pérez ◽

Víctor Dávila-Borja ◽

Silvia Cecilia Pacheco-Velázquez ◽

Javier Alejandro Belmont-Díaz ◽

...

Keyword(s):

Cancer Cells ◽

Cell Cultures ◽

Therapeutic Index ◽

Inhibitory Effect ◽

Cervix Cancer ◽

3T3 Fibroblasts ◽

U373 Cell ◽

Ic50 Values ◽

Anti Inflammatory ◽

Human Cervix

This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC50 = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC50 doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.

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Differential oxidative and pro-apoptotic response of cancer and normal cells to an anti-inflammatory agent CLEFMA

10.1101/2021.06.02.446782 ◽

2021 ◽

Author(s):

Vibhudutta Awasthi ◽

Kaustuv Sahoo

Keyword(s):

Cancer Cells ◽

Survival Data ◽

Maximum Tolerated Dose ◽

Binding Activity ◽

Lung Fibroblasts ◽

Normal Lung ◽

Normal Cells ◽

Dna Binding Activity ◽

Anti Inflammatory

Selective killing of cancer cells by chemotherapy has been an age old challenge, but certain unique features of cancer cells allow discriminatory response between cancer and normal cells. The objectives of this study was to investigate pro-oxidant and apoptotic effects of CLEFMA, an anti-inflammatory compound with anticancer activity, in lung cancer cells versus normal lung fibroblasts and to establish its maximum tolerated dose (MTD) in mice. We found that CLEFMA preferentially induced reactive oxygen species (ROS)-mediated apoptosis in H441, H1650 and H226 cancer cells, but spared normal CCL151 and MRC9 fibroblasts. Immunoblotting studies revealed that CLEFMA-induced apoptosis is associated with p53 phosphorylation in cancer cells which was not observed in CLEFMA treated normal fibroblasts. CLEFMA showed no effect on NF-κB p-65 expression in the normal lung fibroblasts, whereas its translocation to nucleus was inhibited in cancer cells. Furthermore, CLEFMA treatment also inhibited the DNA-binding activity of NF-κB p65 in H441cancer cells, but not in normal CCL151 cells. Preclinical toxicology studies in CD31 mice showed that CLEFMA was not toxic when injected daily for 7 days or injected weekly for 4 weeks. Based on survival data, MTD of CLEFMA was estimated as 30 mg/kg bodyweight. We conclude that CLEFMA exploits the biochemical differences in cancer and normal cells and selectively induces ROS in cancer cells. Secondly, CLEFMA can be safely administered in vivo because its known dose necessary for in vivo efficacy as anti-inflammatory and anti-tumor agent (0.4 mg/kg) is 75 times lower than its MTD.

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Recent Advances Regarding the Therapeutic Potential of Adapalene

Pharmaceuticals ◽

10.3390/ph13090217 ◽

2020 ◽

Vol 13 (9) ◽

pp. 217

Author(s):

Aura Rusu ◽

Corneliu Tanase ◽

Georgiana-Andreea Pascu ◽

Nicoleta Todoran

Keyword(s):

Therapeutic Potential ◽

Biological Effects ◽

Acne Vulgaris ◽

Therapeutic Drug ◽

Oral Drugs ◽

First Line ◽

Biological Potential ◽

Acne Treatment ◽

Anti Inflammatory ◽

Active Substances

Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant Staphylococcus aureus of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combination with other active substances. New topical combinations with adapalene include ketoconazole (antifungal), mometasone furoate (anti-inflammatory corticosteroid), nadifloxacin (fluoroquinolone), and alfa and beta hydroxy acids. Combination with oral drugs is a new trend that enhances the properties of topical formulations with adapalene. Several studies have investigated the effects of ADP in co-administration with azithromycin, doxycycline, faropenem, isotretinoin, and valganciclovir. Innovative formulations of ADP also aim to achieve a better bioavailability, increased efficacy, and reduced side effects. In this review, we have highlighted the current studies on adapalene regarding biological effects useful in various treatment types. Adapalene has not been exploited yet to its full biological potential.

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Polish Propolis—Chemical Composition and Biological Effects in Tongue Cancer Cells and Macrophages

Molecules ◽

10.3390/molecules25102426 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2426 ◽

Cited By ~ 3

Author(s):

Joanna Wezgowiec ◽

Anna Wieczynska ◽

Wlodzimierz Wieckiewicz ◽

Julita Kulbacka ◽

Jolanta Saczko ◽

...

Keyword(s):

Chemical Composition ◽

Cancer Cells ◽

Natural Product ◽

Molecular Mechanisms ◽

Tongue Cancer ◽

Biological Effects ◽

Radical Scavenging ◽

Biological Properties ◽

Gingival Fibroblasts ◽

Anti Inflammatory

The purpose of this study was to compare the chemical composition and biological properties of Polish propolis. Ethanol, ethanol-hexane, hexane and hexane-ethanol extracts of propolis from three different regions of Poland were prepared. On the basis of the evaluation of their chemical composition as well as the extraction yield and free radical scavenging activity, the ethanol and hexane-ethanol extractions were proposed as the most effective methods. Subsequently, the biological properties of the extracts were evaluated to investigate the selectivity of an anticancer effect on tongue cancer cells in comparison to normal gingival fibroblasts. The obtained products demonstrated anticancer activity against tongue cancer cells. Additionally, when the lowest extract concentration (100 µg/mL) was applied, they were not cytotoxic to gingival fibroblasts. Finally, a possible anti-inflammatory potential of the prepared products was revealed, as reduced mitochondrial activity and proliferation of macrophages exposed to the extracts were observed. The results obtained indicate a potential of Polish propolis as a natural product with cancer-selective toxicity and anti-inflammatory effect. However, further studies are still needed to thoroughly explain the molecular mechanisms of its action and to obtain the promising health benefits of this versatile natural product.

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758: Inflammatory and Anti-Inflammatory Regulators alter Levels of an Inhibitor of Apoptosis (IAP), Survivin, in T-24 Bladder Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)30998-4 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 254-254

Author(s):

Justin J. Cohen ◽

Bayan T. Takizawa ◽

Hristos Z. Kaimkliotis ◽

David J. Rosenberg ◽

Marcia A. Wheeler ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Inhibitor Of Apoptosis ◽

Bladder Cancer Cells ◽

Anti Inflammatory

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Antioxidant, antimicrobial, anti-inflammatory and anticancer activities of Carthamus tinctorius flowers

Planta Medica ◽

10.1055/s-0031-1282894 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

NK Bouraoui ◽

S Oueslati ◽

H Falleh ◽

F Harbaoui ◽

R Ksouri ◽

...

Keyword(s):

Carthamus Tinctorius ◽

Anticancer Activities ◽

Anti Inflammatory

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Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

Medicinal Chemistry ◽

10.2174/1573406414666180912105851 ◽

2019 ◽

Vol 15 (5) ◽

pp. 550-560

Author(s):

Mateusz D. Tomczyk ◽

Anna Byczek-Wyrostek ◽

Klaudia Strama ◽

Martyna Wawszków ◽

Przemysław Kasprzycki ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Cell Lines ◽

Inhibitory Activity ◽

Topoisomerase Ii ◽

Significant Activity ◽

Anticancer Activities ◽

Human Colon Cancer ◽

Substitution Pattern ◽

Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

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Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽

10.3390/biom11070957 ◽

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.

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

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00475-0 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13081184 ◽

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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