Development and Evaluation of Ursolic Acid Co-Delivered Tamoxifen Loaded Dammar Gum Nanoparticles to Combat Cancer

2019 ◽  
Vol 11 (11) ◽  
pp. 1115-1124
Author(s):  
Neeraj Sethi ◽  
Prashant Bhardwaj ◽  
Sandeep Kumar ◽  
Neeraj Dilbaghi
Keyword(s):  
Ursolic Acid ◽  
Growth Regulation ◽  
Plant Secondary Metabolites ◽  
Cancer Proliferation ◽  
Pentacyclic Triterpenoid ◽  
Transmission Electron ◽  
Hela Cell Lines ◽  
Anti Cancer ◽  
Anti Oxidant

Therapeutic approaches used to manage cancer, are often associated with drug tolerance or multidrug resistance. The anticancer activity exhibited by plant secondary metabolites can be effectively enhanced by formulating them at nanometric scale. Ursolic acid (UA) is a pentacyclic triterpenoid that reduces cancer proliferation by interfering cell growth regulation. Tamoxifen (TAM) is an adjuvant molecule employed for hormonal therapy of cancer especially breast cancer. To improve the bioavailability and synergism, UA and TAM loaded Dammar gum nanoparticles (UTDNPs) were prepared in current study by employing oil in oil (O/O) emulsion solvent evaporation method. Zeta potential value of UTDNPs was found to be +23 mV demonstrating relative stability of nanoformulation. The percentage encapsulation efficiency value was found to be 72.5% for UA and 76.6% for TAM. The UTDNPs posses particle size in the range of 45–55 nm as revealed by transmission electron microscopy. The UTDNPs showed sustained release and their anti-oxidant and anti-cancer potential was much more pronounced than free UA and TAM particles alone. The in vitro studies demonstrated that UA and TAM encapsulated in dammar gum inhibited growth of A-549, MCF-7, and Hela cell lines more effectively than UA and TAM alone which proved their robust anticancer potential.

scholarly journals Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4424
Author(s):  
Uzma Arshad ◽  
Sibtain Ahmed ◽  
Nusrat Shafiq ◽  
Zaheer Ahmad ◽  
Aqsa Hassan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Catalytic Amount ◽  
Pyrimidine Derivatives ◽  
Qsar Studies ◽  
Lead Compounds ◽  
Biological Potential ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Vitro Analysis

Objective: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. Methodology: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. Results: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

Design and synthesis of novel benzimidazoles containing 1,2,3-triazolesas in vitro, anticancer and anti-oxidant agents

2021 ◽  
Vol 25 (11) ◽  
pp. 104-109
Author(s):  
Gullapelli Kumaraswamy ◽  
Ravichandar Maroju ◽  
Srinivas Bandari ◽  
Gouthami Dasari ◽  
Gullapelli Sadanandam
Keyword(s):  
Spectroscopic Methods ◽  
Moderate Activity ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Excellent Activity ◽  
Test Organisms ◽  
Anti Oxidant ◽  
High Yields ◽  
Cancer Activity

A novel series of 2-(1-((1-substitutedphenyl-1H-1,2,3- triazol-4-yl)methoxy)ethyl)-1-((1-substituted phenyl- 1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (3a-j)derivatives was synthesized in moderate to high yields. The structures of all the synthesized compounds were characterized by 1HNMR, 13CNMR and Mass spectroscopic methods. The title compounds were screened for their anti-oxidant activity and anti-cancer activity. The cancer activity results reveal that the compounds 3j, 3b and 3f are showing promising activity and remaining compounds exhibited moderate activity against all the tested cancer cell lines. The anti-oxidant activity also shows that the compounds 3c and 3d have shown excellent activity and remaining compounds were also found to exhibit moderate activity against the test organisms employed.

scholarly journals Considerable Improvement of Ursolic Acid Water Solubility by Its Encapsulation in Dendrimer Nanoparticles: Design, Synthesis and Physicochemical Characterization

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2196 ◽  
Author(s):  
Silvana Alfei ◽  
Anna Maria Schito ◽  
Guendalina Zuccari
Keyword(s):  
Ursolic Acid ◽  
Water Solubility ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Systemic Toxicity ◽  
Water Soluble ◽  
Design Synthesis ◽  
Pentacyclic Triterpenoid

Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

Delivery of Ursolic Acid by Polyhydroxybutyrate Nanoparticles for Cancer Therapy: in silico and in vitro Studies

Drug Research ◽  
2021 ◽  
Author(s):  
Sureshbabu Ram Kumar Pandian ◽  
Selvaraj Kunjiappan ◽  
Parasuraman Pavadai ◽  
Velmurugan Sundarapandian ◽  
Vivek Chandramohan ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Growth Factor Receptor ◽  
Maximum Efficiency ◽  
Release Behavior ◽  
Drug Release Behavior ◽  
Pentacyclic Triterpenoid ◽  
Epidermal Growth ◽  
Uv Visible ◽  
Average Size

AbstractUrsolic acid (UA), a pentacyclic triterpenoid and a phytochemical, is a potent inhibitory agent against proliferation of various tumors. Polyhydroxybutyrate nanoparticles (PHB NPs) are preferred in therapeutics due to their drug-stabilizing property and enhanced biological activity. In this study, PHB NPs were utilized to deliver and enhance the bioavailability of UA against cancer cells (HeLa). Further, molecular docking and dynamic studies were conducted to calculate the binding affinity and stability of UA at the active site of target protein (epidermal growth factor receptor-EGFR). The PHB NPs revealed the average size as 150–200 nm in TEM, which were used in subsequent experiments. The cytoplasmic uptake of nanoparticles was confirmed by florescent microscopy. The encapsulation potential of PHB NPs with UA was assessed by UV–visible spectrophotometer as 54%. Besides, the drug release behavior, cytotoxicity and the regulation of apoptosis were investigated in vitro. The cytotoxicity results revealed that the maximum efficiency of drug delivery was at 96th hour.

scholarly journals In Vitro Anticancer Properties of Copper Metallodendrimers

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 155 ◽  
Author(s):  
Hołota ◽  
Magiera ◽  
Michlewska ◽  
Kubczak ◽  
del Olmo ◽  
...  
Keyword(s):  
Fluorescence Anisotropy ◽  
Drug Carriers ◽  
Haemolytic Activity ◽  
Surface Groups ◽  
Biological Processes ◽  
Normal Cells ◽  
Anticancer Properties ◽  
Transmission Electron ◽  
Anti Cancer

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells.

scholarly journals The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 427 ◽  
Author(s):  
Ranjini Sankaranarayanan ◽  
Chaitanya Valiveti ◽  
D. Kumar ◽  
Severine Van slambrouck ◽  
Siddharth Kesharwani ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell Proliferation ◽  
Cyclin Dependent Kinase ◽  
Specific Amino Acid ◽  
In Silico Studies ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
First Time ◽  
Related Compounds

Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that orientation of the functional groups and specific amino acid interactions may play a role in inhibition. We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation. These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC.

scholarly journals Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

2020 ◽  
Vol 21 (16) ◽  
pp. 5920 ◽  
Author(s):  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe
Keyword(s):  
Ursolic Acid ◽  
Clinical Medicine ◽  
Biological Activities ◽  
Therapeutic Effects ◽  
Pharmacological Activities ◽  
Pentacyclic Triterpenoid ◽  
Anti Cancer ◽  
Pharmacologically Active ◽  
Derivatives Of ◽  
Cell Signaling Pathways

Ursolic acid is a pharmacologically active pentacyclic triterpenoid derived from medicinal plants, fruit, and vegetables. The pharmacological activities of ursolic acid have been extensively studied over the past few years and various reports have revealed that ursolic acid has multiple biological activities, which include anti-inflammatory, antioxidant, anti-cancer, etc. In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid. These structurally modified compounds display enhanced therapeutic effects when compared to ursolic acid. This present review summarizes various synthesized derivatives of ursolic acid with anti-cancer activity which were reported from 2015 to date.

IN VIVO AND IN VITRO EVALUATION OF ANTI-CANCER ACTIVITY OF NEWLY SYNTHESIZED COBALT COMPLEX OF COUMARIN SCHIFF BASES

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (04) ◽  
pp. 61-69
Author(s):  
A. Rayaji ◽  
A. H. M. Viswanatha Swamy ◽  
Keyword(s):  
Nitric Oxide ◽  
Hepg2 Cell ◽  
Cobalt Complex ◽  
Reducing Ability ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Hepg2 Cell Lines ◽  
Cancer Activity

Hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocytes. Modern treatment of cancer includes chemotherapy, hormone therapy, radiotherapy and surgery but they are associated with several adverse effects such as alopecia, fatigue and general weakening of the body’s immune system due to bone marrow suppression. However, there is a continual need to look out for newer drugs to overcome the menace of cancer. In view of this we synthesized the new Coumarin-Cobalt complex derivatives. Structures of all the newly synthesized metal complexes are supported by Spectral data such as IR, NMR, and mass spectrometry. Coumarin-Cobalt complex of vanillin exhibited significant anti-cancer activity by in vivo anticancer activity (BrdU estimation). Immunohistochemical analysis has been done by BrdU and the synthesized compounds were screened for anti-oxidant activity and in vitro HepG2 cell lines. The IC50 values of the HepG2 cell lines as compared with that of standard Cisplatin and compounds IIIb, IIId, IIIe, IIIh and IIIj showed appreciable activity at a concentration less than 10 μG. Coumarin-Cobalt complex of vanillin exhibited significant anti-cancer activity. Anti-oxidant activity performed by Nitric oxide reducing ability, Superoxide dismutase and reducing activity:Compounds IIIc, IIIe and IIIg showed appreciable activity at 400μg/mL and 800 μg/mL screened by nitric oxide reducing ability, superoxide anion was effectively scavenged by compound IIIg at 400μg/mL and 800 μg/mL and reducing power of compounds IIIc and IIIj is comparable with standard ascorbic acid at concentrations 400μg/mL and 800 μg/mL.

scholarly journals The Implication of Chemotypic Variation on the Anti-Oxidant and Anti-Cancer Activities of Sutherlandia frutescens (L.) R.Br. (Fabaceae) from Different Geographic Locations

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 152
Author(s):  
Samkele Zonyane ◽  
Olaniyi A. Fawole ◽  
Chris la Grange ◽  
Maria A. Stander ◽  
Umezuruike L. Opara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Radical Scavenging ◽  
Western Cape ◽  
Dpph Radical ◽  
Anti Cancer ◽  
Northern Cape ◽  
Anti Oxidant ◽  
Dpph Radical Scavenging ◽  
Sutherlandia Frutescens

Extracts of Sutherlandia frutescens (cancer bush) exhibit considerable qualitative and quantitative chemical variability depending on their natural wild origins. The purpose of this study was thus to determine bioactivity of extracts from different regions using in vitro antioxidant and anti-cancer assays. Extracts of the species are complex and are predominantly composed of a species-specific set of triterpene saponins (cycloartanol glycosides), the sutherlandiosides, and flavonoids (quercetin and kaempferol glycosides), the sutherlandins. For the Folin-Ciocalteu phenolics test values of 93.311 to 125.330 mg GAE/g DE were obtained. The flavonoids ranged from 54.831 to 66.073 mg CE/g DE using the aluminum chloride assay. Extracts from different sites were also assayed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging method and ferric reducing anti-oxidant power (FRAP) methods. This was followed by an in vitro Cell Titer-Glo viability assay of various ecotypes using the DLD-1 colon cancer cell line. All test extracts displayed anti-oxidant activity through the DPPH• radical scavenging mechanism, with IC50 values ranging from 3.171 to 7.707 µg·mL−1. However, the degree of anti-oxidant effects differed on a chemotypic basis with coastal plants from Gansbaai and Pearly Beach (Western Cape) exhibiting superior activity whereas the Victoria West inland group from the Northern Cape, consistently showed the weakest anti-oxidant activity for both the DPPH• and FRAP methods. All extracts showed cytotoxicity on DLD-1 colon cancer cells at the test concentration of 200 µg·mL−1 but Sutherlandia plants from Colesburg (Northern Cape) exhibited the highest anti-cancer activity. These findings confirm that S. frutescens specimens display variability in their bioactive capacities based on their natural location, illustrating the importance of choosing relevant ecotypes for medicinal purposes.

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