scholarly journals Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

2021 ◽  
Vol 22 (11) ◽  
pp. 5678
Author(s):  
Anna Aviñó ◽  
Anna Clua ◽  
Maria José Bleda ◽  
Ramon Eritja ◽  
Carme Fàbrega
Keyword(s):  
Folic Acid ◽  
Cellular Uptake ◽  
Antiproliferative Activity ◽  
Biological Effects ◽  
Metabolic Activation ◽  
Receptor Ligands ◽  
Short Oligonucleotide ◽  
Anti Cancer ◽  
Small Molecule Enhancers ◽  
Oligonucleotide Conjugates

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.

Fluorescent Copper(II) Complexes of Asymmetric Bis(Thiosemicarbazone)s: Electrochemistry, Cellular Uptake and Antiproliferative Activity

2021 ◽  
Vol 6 (24) ◽  
pp. 6063-6070
Author(s):  
Deepti U. Kirtani ◽  
Niraj S. Ghatpande ◽  
Komal R. Suryavanshi ◽  
Prasad P. Kulkarni ◽  
Anupa A. Kumbhar
Keyword(s):  
Cellular Uptake ◽  
Antiproliferative Activity

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

scholarly journals Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

2018 ◽  
Vol 19 (11) ◽  
pp. 3403 ◽  
Author(s):  
Xu Hu ◽  
Dahong Li ◽  
Chun Chu ◽  
Xu Li ◽  
Xianhua Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Natural Products ◽  
Drug Administration ◽  
Antiproliferative Activity ◽  
Natural Source ◽  
Antiproliferative Effects ◽  
Anti Cancer ◽  
Ring Structures ◽  
First Time ◽  
Antiproliferative Activities

Alkaloids, a category of natural products with ring structures and nitrogen atoms, include most U.S. Food and Drug Administration approved plant derived anti-cancer agents. Evodiamine is an alkaloid with attractive multitargeting antiproliferative activity. Its high content in the natural source ensures its adequate supply on the market and guarantees further medicinal study. To the best of our knowledge, there is no systematic review about the antiproliferative effects of evodiamine derivatives. Therefore, in this article the review of the antiproliferative activities of evodiamine will be updated. More importantly, the antiproliferative activities of structurally modified new analogues of evodiamine will be summarized for the first time.

scholarly journals Folic acid – role in the body, recommendations and clinical significance

2019 ◽  
Vol 18 (1) ◽  
pp. 50-59 ◽  
Author(s):  
Aneta Myszczyszyn ◽  
Rafał Krajewski ◽  
Monika Ostapów ◽  
Lidia Hirnle
Keyword(s):  
Folic Acid ◽  
Biological Effects ◽  
Folic Acid Supplementation ◽  
The Body ◽  
Leafy Vegetables ◽  
Congenital Defects ◽  
Natural Form ◽  
Vitamin B9 ◽  
Increased Risk

AbstractIntroduction. Folic acid is a compound classified as B group vitamins. In the body it is subject to processes that transfer its inactive form into a form responsible for biological effects of folic acid, i.e. 5-methyltetrahydrofolate (5-MTHF). It is, in particular, responsible for processes of the correct biosynthesis of purine and pyridine bases present in the formation of DNA and RNA molecules. Humans do not synthesize the endogenous form of folic acid; therefore, it is vital to supplement this vitamin in its natural form or multivitamin preparations. The most folic acid is found in the green leafy vegetables (spinach, peas, asparagus) and in offal (liver). An adequate supply of folic acid is especially indicated in pregnant women with a reduced amount of folic acid due to its use by an intensively developing foetus. The recommended dose of folic acid during this period is 0.4 mg/24h and this dose varies depending on the patient’s and her family’s medical history. The updated state of knowledge on the role of vitamin B9 in the body has been presented. The importance of its supplementation in specific clinical cases was analyzed.Summary. Many studies indicate an important role of the folic acid in the prevention of congenital defects of the nervous, cardiovascular and urogenital systems. Its deficiency increases the risk of complications in pregnancy, such as recurrent miscarriages, pre-eclampsia or postpartum haemorrhage. For this reason, a prophylactic folic acid supplementation is recommended, in women with increased risk of its deficiency, in particular.

The Molecular targets of Cannabinoids in the treatment of Cancer and Inflammation

2021 ◽  
Vol 27 ◽  
Author(s):  
Alenabi Aylar ◽  
Malekinejad Hassan
Keyword(s):  
Cannabinoid Receptors ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Anticancer Effects ◽  
Anti Cancer ◽  
Culture Models ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Objective: In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas and hepatic cancers. The anticancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cells migration, suppression of vascularization and induction of apoptosis. Conclusion: The current review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

scholarly journals Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus.

1996 ◽  
Vol 40 (7) ◽  
pp. 1670-1675 ◽  
Author(s):  
Y Shoji ◽  
J Shimada ◽  
Y Mizushima ◽  
A Iwasawa ◽  
Y Nakamura ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Cellular Uptake ◽  
Biological Effects ◽  
Laser Scanning Microscopy ◽  
Antisense Oligodeoxynucleotide ◽  
Acceptor Site ◽  
Simplex Virus ◽  
Hsv 1

In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect in cells infected with HSV-1 or HSV-2 was assessed and compared with the cellular uptake of the analog. We found that antisense S-ODNs showed the most potent antiherpetic activity, with 50% inhibitory concentrations of 5 microM for HSV-1 and 0.25 microM for HSV-2. The antiviral effect of antisense S-ODNs was stronger and longer acting than that of acyclovir. Cell association of S-ODNs was the highest and paralleled antiviral activity. Furthermore, some fluorescein isothiocyanate (FITC)-labeled S-ODNs were recognized in the nuclei in HSV-1 infected cells by confocal laser scanning microscopy. S-ODNs located in the nucleus could access the targeted mRNA, which might be responsible for the antiviral activities. Although our study also showed non-sequence-specific activity, which implies that multiple mechanisms are involved, S-ODNs are a promising novel anti-herpetic agent.

scholarly journals Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 522 ◽  
Author(s):  
Vanessa T. Chivere ◽  
Pierre P. D. Kondiah ◽  
Yahya E. Choonara ◽  
Viness Pillay
Keyword(s):  
Oral Delivery ◽  
Oral Drug Delivery ◽  
Specific Binding ◽  
Biological Effects ◽  
Aqueous Solubility ◽  
Oral Route ◽  
Oral Drug ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Route Of Delivery

Routes of drug administration and their corresponding physiochemical characteristics play major roles in drug therapeutic efficiency and biological effects. Each route of delivery has favourable aspects and limitations. The oral route of delivery is the most convenient, widely accepted and safe route. However, the oral route of chemotherapeutics to date have displayed high gastric degradation, low aqueous solubility, poor formulation stability and minimum intestinal absorption. Thus, mainstream anti-cancer drugs in current formulations are not suitable as oral chemotherapeutic formulations. The use of biopolymers such as chitosan, gelatin, hyaluronic acid and polyglutamic acid, for the synthesis of oral delivery platforms, have potential to help overcome problems associated with oral delivery of chemotherapeutics. Biopolymers have favourable stimuli-responsive properties, and thus can be used to improve oral bioavailability of anti-cancer drugs. These biopolymeric formulations can protect gastric-sensitive drugs from pH degradation, target specific binding sites for targeted absorption and consequently control drug release. In this review, the use of various biopolymers as oral drug delivery systems for chemotherapeutics will be discussed.

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