- Probing the Interaction of Newly Synthesized Pt(II) Complex on Human Serum Albumin Using Competitive Binding Site Markers. [Journal Article]
- JFJ Fluoresc 2019 Jun 19
- Considering the importance of pharmacology and the influence of drugs on biological materials, the effects of a newly designed and synthesized platin complex (2,2'-Bipyridine-3,3'-dicarboxylic acid, …
Considering the importance of pharmacology and the influence of drugs on biological materials, the effects of a newly designed and synthesized platin complex (2,2'-Bipyridine-3,3'-dicarboxylic acid, oxalato Platinum(II), as an antitumor drug was tested on the structure of blood carrier protein of human serum albumin (HSA) using various spectroscopic techniques including UV-visible, fluorescence, and circular dichroism at 25 and 37 °C. Results of the fluorescence measurements revealed that adding the complex caused reduction in intrinsic fluorescence emission of HSA resulted from dynamic quenching of HSA. The number of binding sites and binding constants were calculated at both temperatures of 25 and 37 °C. In addition, in order to identify the complex's binding site on HSA employing spectroscopy, the competitive studies were followed using warfarin, digitoxin and ibuprofen as site markers of Sudlow sites I, II and III. Competitive binding test results have shown that Pt(II) complex bind on the warfarin binding site (or Sudlow sites I) on HSA. Besides, a reduction in thermal stability for HSA was observed in the presence of the newly designed Pt(II) complex.
- Cardiac Glycosides in Human Physiology and Disease: Update for Entomologists. [Review]
- IInsects 2019 Apr 10; 10(4)
- Cardiac glycosides, cardenolides and bufadienolides, are elaborated by several plant or animal species to prevent grazing or predation. Entomologists have characterized several insect species that ha…
Cardiac glycosides, cardenolides and bufadienolides, are elaborated by several plant or animal species to prevent grazing or predation. Entomologists have characterized several insect species that have evolved the ability to sequester these glycosides in their tissues to reduce their palatability and, thus, reduce predation. Cardiac glycosides are known to interact with the sodium- and potassium-activated adenosine triphosphatase, or sodium pump, through a specific receptor-binding site. Over the last couple of decades, and since entomologic studies, it has become clear that mammals synthesize endogenous cardenolides that closely resemble or are identical to compounds of plant origin and those sequestered by insects. The most important of these are ouabain-like compounds. These compounds are essential for the regulation of normal ionic physiology in mammals. Importantly, at physiologic picomolar or nanomolar concentrations, endogenous ouabain, a cardenolide, stimulates the sodium pump, activates second messengers, and may even function as a growth factor. This is in contrast to the pharmacologic or toxic micromolar or milimolar concentrations achieved after consumption of exogenous cardenolides (by consuming medications, plants, or insects), which inhibit the pump and result in either a desired medical outcome, or the toxic consequence of sodium pump inhibition.
- Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study. [Journal Article]
- EJEur J Heart Fail 2019; 21(5):676-684
- CONCLUSIONS: The DIGIT-HF trial will provide important evidence, whether the cardiac glycoside digitoxin reduces the risk for all-cause mortality and/or hospital admission for worsening HF in patients with advanced chronic HFrEF on top of standard of care treatment.
- Unravelling the interaction mechanism between clioquinol and bovine serum albumin by multi-spectroscopic and molecular docking approaches. [Journal Article]
- SASpectrochim Acta A Mol Biomol Spectrosc 2019 Jun 05; 216:25-34
- Clioquinol has recently been proposed for the treatment of Alzheimer's disease. It is able to diminish β-amyloid protein aggregation and to restore cognition of Alzheimer's mice. However, its therape…
Clioquinol has recently been proposed for the treatment of Alzheimer's disease. It is able to diminish β-amyloid protein aggregation and to restore cognition of Alzheimer's mice. However, its therapeutic benefits for Alzheimer's disease in human remain controversy and need further confirmation. Herein, we have explored the interaction mechanism of clioquinol toward bovine serum albumin (BSA) by means of multi-spectroscopic and docking simulation approaches. Clioquinol interacts with BSA by a combined mechanism of static and dynamic processes. Application of the Hill's equation to fluorescence quenching experiment revealed that the binding constant of the BSA-clioquinol complex is extremely high at 108 M-1 level. Competitive displacement and docking analysis consistently suggested that there are the multiple binding modes of clioquinol toward BSA. Competitive binding study showed that clioquinol shares the binding sites with ibuprofen and digitoxin on albumin, referring to be site II and site III binding compounds. Besides, partial binding in site I was also observed. Docking simulation confirmed that clioquinol favors to bind in site I, site II, site III, fatty acid binding site 5, and the protein cleft between subdomain IB and IIIB of the BSA. Due to its small size and electric dipole property, clioquinol may easily fit in multiple pockets of the BSA. Our finding suggests the potential role of BSA as a clioquinol carrier in the vascular system. Nonetheless, clioquinol-induced BSA aggregation has been observed by the three-dimensional fluorescence technique. This phenomenon may not only impair the BSA, but may also affect other endogenous proteins, which eventually causes adverse effects to human. Therefore, the redesigned or modified molecular structure of clioquinol may reduce its toxicity and improve its bioavailability.
- Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives. [Journal Article]
- EJEur J Med Chem 2019 Apr 01; 167:546-561
- In recent years, new therapeutic possibilities were proposed for cardiac glycosides traditionally used to treat heart diseases, such as anticancer and antiviral activities. In this sense, this work a…
In recent years, new therapeutic possibilities were proposed for cardiac glycosides traditionally used to treat heart diseases, such as anticancer and antiviral activities. In this sense, this work aimed to synthesize the readily accessible 3β-azido-3-deoxydigitoxigenin (5) from digitoxigenin (1). Two new series of compounds were obtained from derivative (5): (i) O-glycosyl trizols through click chemistry with propargyl glycosides; and (ii) compounds substituted in the alpha carbonyl position with different residues linked via an amino-group. All obtained derivatives have their chemical structures confirmed, and their anti-herpes (against HSV-types 1 and 2 replication) and cytotoxic (against PC3, A549, HCT-8 and LNCaP cell lines) activities evaluated. Compounds 10 and 11 exhibited the most promising results against HSV-1 (KOS and 29-R strains) and HSV-2 (333 strain) replication with SI values > 1000. Both compounds were also the most cytotoxic for the human cancer cell lines tested with IC50 values similar to those of paclitaxel. They also presented reduced toxicity toward non-cancerous cell lines (MRC-5 and HGF cells). Promising compounds were tested in regard to their ability to inhibit Na+/K+-ATPase. The inhibition rate correlates suitably with the bioactivity demonstrated by those both compounds against the different human cancer cells tested as well as against HSV replication. Moreover, the results showed that specific chemical features of compound 10 and 11 influenced the bioactivities tested. In summary, it was possible to obtain novel digitoxigenin-derivatives with remarkable cytotoxic and anti-herpes activities as well as low toxicity and high selectivity. In this way, they could be considered potential molecules for the development of new drugs.
- StatPearls: Cardioactive Steroid Toxicity [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Cardioactive steroids (CAS) are medically important compounds historically used for conditions like edema and "dropsy." There is literature from the 17th century regarding their therapeutic effects. …
Cardioactive steroids (CAS) are medically important compounds historically used for conditions like edema and "dropsy." There is literature from the 17th century regarding their therapeutic effects. They are available in several plants including oleander, foxglove, lily of the valley, red squill, dogbane, common milkweed plant, etc. Leaves of Digitalis lanata contain digoxin while seeds of Digitalis purpurea may contain digitalin. Several Chinese herbal medications and aphrodisiacs may also contain cardioactive steroids. Historians believe the selection of yellow contrast in Van Gogh's painting was likely secondary to digitalis toxicity. Digoxin is the most well known cardioactive steroid with application in the treatment of congestive heart failure and for the control of ventricular rate in atrial tachyarrhythmias. It is available in tablet form and liquid filled capsules that can increase its bioavailability. Other less commonly used cardioactive steroids include lanatoside C, digitoxin, ouabain, gitalin, and deslanoside.
- Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis. [Journal Article]
- PPhytomedicine 2018 Dec 01; 51:162-170
- CONCLUSIONS: Periplocin displays a promising mechanism of action in sarcoma cells because altering the death receptor expression is an interesting target in sarcoma treatment especially to overcome TRAIL resistance.
- Digitoxin Suppresses Store Operated Calcium Entry by Modulating Phosphorylation and the Pore Region of Orai1. [Journal Article]
- CMCurr Mol Med 2018; 18(6):392-399
- CONCLUSIONS: Our study identified two regions that are critical for the inhibition on Orai1 channels, providing valuable hotspots for future design of SOCE inhibitors.
- Overgangen fra digitoksin til digoksin i årene 2011–13. [Journal Article]
- TNTidsskr Nor Laegeforen 2018 10 02; 138(15)
- The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to follow individual patients during …
The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to follow individual patients during the switch.
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- Fra digitoksin til digoksin. [Editorial]
- TNTidsskr Nor Laegeforen 2018 10 02; 138(15)