scholarly journals Toxic Effects of Metallopharmaceuticals

2017 ◽  
Vol 18 (3) ◽  
pp. 191-194 ◽  
Author(s):  
Slobodan Novokmet ◽  
Isidora Stojic ◽  
Katarina Radonjic ◽  
Maja Savic ◽  
Jovana Jeremic
Keyword(s):  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Anticancer Agents ◽  
Rational Design ◽  
Current Knowledge ◽  
The Past ◽  
Ru Complexes ◽  
Key Features

Abstract Discovery of the metallopharmaceutical cisplatin and its use in antitumour therapy has initiated the rational design and screening of metal-based anticancer agents as potential chemotherapeutics. In addition to the achievements of cisplatin and its therapeutic analogues, there are significant drawbacks to its use: resistance and toxicity. Over the past four decades, numerous transition metal complexes have been synthesized and investigated in vitro and in vivo. The most studied metals among these complexes are platinum and ruthenium. The key features of these investigations is to find novel metal complexes that could potentially exert less toxicity and equal or higher antitumour potency and to overcome other pharmacological deficiencies. Ru complexes have a different mode of action than cisplatin does, some of which are under clinical trials for treating metastatic or cisplatin-resistant tumours. This review consists of the current knowledge, published and unpublished, related to the toxicity of metallopharmaceuticals, and special attention is given to platinum [Pt(II) and Pt(IV)] and ruthenium [Ru(II) and Ru(III)] complexes.

scholarly journals Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1412
Author(s):  
Maria Grazia Ferraro ◽  
Marialuisa Piccolo ◽  
Gabriella Misso ◽  
Francesco Maione ◽  
Daniela Montesarchio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Preclinical Development ◽  
Cell Death Pathways ◽  
Complex Information ◽  
Ru Complexes ◽  
Therapeutic Alternatives

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

scholarly journals The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart

2017 ◽  
Vol 18 (2) ◽  
pp. 111-117
Author(s):  
Katarina Radonjic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Nevena Jeremic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Rat Heart ◽  
Clinical Success ◽  
Chemotherapeutic Agents ◽  
Isolated Rat Heart

AbstractInterest for the clinical application of transition metal complexes as chemotherapeutic agents initially started with discovery of cisplatin. Despite the remarkable clinical success, cisplatin treatment is limited due to its resistance and side effects. Over the last 40 years, numerous transition metal complexes were synthesized and investigated in vitro and in vivo in order to establish a metallopharmaceutical that will exert less toxicity and equal or higher potency. We have compared the cardiotoxicity of 2 platinum complexes, one ligand, and a starting salt for complex synthesis using an experimental model of an isolated, perfused rat heart according to the Langendorfftechnique. The cardiotoxicity was assessed by comparison of oxidative stress induced following the perfusion of the following compounds: Dichloro(1,2-diaminocyclohexane)platinum(II), cisplatin, potassium-tetra-chloroplatinum(II) and 1,2-diaminocyclohexane, which were perfused at increasing concentrations from 10−8to 10−4M for 30 minutes. The oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, thiobarbituric acid reactive substances, and nitric oxide from the coronary venous effluent. Our results showed that the levels of oxidative stress parameters were not significantly affected by perfusion with all the tested compounds and were not dose-dependent. These results could be of importance to further investigations concerning the effects of platinum-based potential anticancer drugs on the heart.

scholarly journals PPAR and Agonists against Cancer: Rational Design of Complementation Treatments

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Dorina Veliceasa ◽  
Frank Thilo Schulze-Hoëpfner ◽  
Olga V. Volpert
Keyword(s):  
Rational Design ◽  
Current Knowledge ◽  
Vascular Complications ◽  
Recent Decade ◽  
Cell Types ◽  
Insulin Sensitizers ◽  
Ppar Agonists ◽  
Multiple Cell

PPAR is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPAR has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPAR role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPAR image as potential anticancer drug. Currently PPAR is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPAR and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPAR regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPAR agonists.

scholarly journals Recent advances in cancer photo-theranostics: the synergistic combination of transition metal complexes and gold nanostructures

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Loredana Ricciardi ◽  
Massimo La Deda
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Biomedical Application ◽  
Light Exposure ◽  
Gold Nanostructures ◽  
First Choice ◽  
Cancer Theranostics

AbstractIn this mini review, we highlight advances in the last five years in light-activated cancer theranostics by using hybrid systems consisting of transition metal complexes (TMCs) and plasmonic gold nanostructures (AuNPs). TMCs are molecules with attractive properties and high potential in biomedical application. Due to their antiproliferative abilities, platinum-based compounds are currently first-choice drugs for the treatment of several solid tumors. Moreover, ruthenium, iridium and platinum complexes are well-known for their ability to photogenerate singlet oxygen, a highly cytotoxic reactive species with a key role in photodynamic therapy. Their potential is further extended by the unique photophysical properties, which make TMCs particularly suitable for bioimaging. Recently, gold nanoparticles (AuNPs) have been widely investigated as one of the leading nanomaterials in cancer theranostics. AuNPs—being an inert and highly biocompatible material—represent excellent drug delivery systems, overcoming most of the side effects associated with the systemic administration of anticancer drugs. Furthermore, due to the thermoplasmonic properties, AuNPs proved to be efficient nano-sources of heat for photothermal therapy application. Therefore, the hybrid combination TMC/AuNPs could represent a synergistic merger of multiple functionalities for combinatorial cancer therapy strategies. Herein, we report the most recent examples of TMC/AuNPs systems in in-vitro in-vivo cancer tharanostics application whose effects are triggered by light-exposure in the Vis–NIR region, leading to a spatial and temporal control of the TMC/AuNPs activation for light-mediated precision therapeutics.

Hybrid Molecules with Potential Activity against Drug-resistant Cancer – PART-I

2021 ◽  
Vol 21 (19) ◽  
pp. 1711-1711
Author(s):  
Lian-Shun Feng
Keyword(s):  
Anticancer Agents ◽  
Intracellular Signaling ◽  
Hydroxamic Acid ◽  
Rational Design ◽  
Tumor Therapy ◽  
The Body ◽  
Drug Resistant ◽  
Hybrid Molecules

Cancer, which can invade almost all parts of the body, accounts for 18% of all deaths throughout the world and ranks as one of the leading causes of death among non-communicable diseases [1, 2]. Since cancers have a high chance of curing if appropriate treatment is provided, anticancer agents are critical for tumor therapy. However, the continuous emergency of drug-resistant cancer has already become one of the major challenges in the control and eradication of cancers [3, 4]. Therefore, dis-covering the next wave of anticancer agents with high potency against drug-resistant forms is vital. Coumarin, podophyllotoxin, hydroxamic acid, ferrocene, and acridine derivatives cannot only in-hibit tumor proliferation, invasion, and metastasis by acting on multiple intracellular signaling net-work molecules but also have reverse cancer multidrug resistance effect [5-9]. Moreover, many cur-rent available anticancer agents own these pharmacophores, demonstrating the potential of these pharmacophores to fight against various cancers, including drug-resistant forms. Hybridization repre-sents a promising strategy to develop novel anticancer agents since hybrid molecules can simultaneously act on dual or multi-ple cancer-relevant targets, such as metalloproteinases, ATP binding cassette subfamily G member 2 (ABCG2), human mito-chondrial peptide deformylase, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), P-glycoprotein (P-gp), tubulin, and vascular endothelial growth factor (VEGF) [10, 11]. Thus, hybrid molecules can increase specificity, reduce side effects, improve patient compliance, and overcome drug resistance [12]. Accordingly, a combination of coumarin, podophyl-lotoxin, hydroxamic acid, ferrocene, or acridine with other anticancer pharmacophores is an attractive strategy for the discov-ery of novel anticancer agents with potent activity against various cancers, especially drug-resistant forms. This special issue focuses on the current scenario of coumarin, podophyllotoxin, hydroxamic acid, ferrocene, and acridine hybrids with in vitro and in vivo anticancer potential. The mechanisms of action, the critical aspects of design, and structure-activity relationships are also discussed to pave the way for the further rational design of novel candidates with excellent effi-ciency against drug-resistant cancers.

scholarly journals Tumorcode - A framework to simulate vascularized tumors

2017 ◽  
Author(s):  
Thierry Fredrich ◽  
Michael Welter ◽  
Heiko Rieger
Keyword(s):  
Computer Simulations ◽  
Current Knowledge ◽  
Complex Interaction ◽  
Biological Models ◽  
The Public ◽  
Multi Scale ◽  
Simulation Procedure ◽  
The Past

AbstractDuring the past years our group published several articles using computer simulations to address the complex interaction of tumors and the vasculature as underlying transport network. Advances in imaging and lab techniques pushed in vitro research of tumor spheroids forward and animal models as well as clinical studies provided more insights to single processes taking part in tumor growth, however, an overall picture is still missing. Computer simulations are a none-invasive option to cumulate current knowledge and form a quasi in vivo system. In our software, several known models were assembled into a multi-scale approach which allows to study length scales relevant for clinical applications.We release our code to the public domain, together with a detailed description of the implementation and several examples, with the hope of usage and futher development by the community. Justification for the included algorithms and the biological models was obtained in previous publications, here we summarize technical aspects following the workflow of a typical simulation procedure.

Exposing “Bright” Metals: Promising Advances in Photoactivated Anticancer Transition Metal Complexes

2018 ◽  
Vol 25 (4) ◽  
pp. 478-492 ◽  
Author(s):  
Aleksandra Bjelosevic ◽  
Benjamin J. Pages ◽  
Lawson K. Spare ◽  
Krishant M. Deo ◽  
Dale L. Ang ◽  
...  
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Molecular Geometry ◽  
In Vitro Cytotoxicity ◽  
Selective Treatment ◽  
Chemotherapy Drugs ◽  
Recent Advances

Background: Photodynamic therapy (PDT) is an increasingly prominent field in anticancer research. PDT agents are typically nontoxic in the absence of light and can be stimulated with nonionising irradiation to “activate” their cytotoxic effect. Photosensitzers are not classified as chemotherapy drugs although it is advantageous to control the toxicity of a drug through localised irradiation allowing for selective treatment. Transition metals are an extremely versatile class of compounds with various unique properties such as oxidation state, coordination number, redox potential and molecular geometry that can be tailored for specific uses. This makes them excellent PDT candidates as their properties can be manipulated to absorb a specific range of light wavelengths, cross cellular membranes or target specific sites in vitro. This article reviews recent advances in transition metal PDT agents, with a focus on structural scaffolds from which several metal complexes in a series are synthesised, as well as their in vitro cytotoxicity in the presence or absence of irradiation. Conclusion: The success of clinical photoactive agents such as Photofrin® has inspired the development of thousands of potential PDT agents. Transition metal complexes in particular have demonstrated excellent versatility and diversity when it comes to PDT for treatment of invasive cancers. This review has highlighted some of the many recent advances of transition metal PDT agents with high in vitro and in vivo phototoxic activity. Photoactive transition metal complexes have proven their potential due to their inherent physicochemical variety, allowing them to fill a niche in the PDT world.

The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents

2020 ◽  
Vol 20 (18) ◽  
pp. 2216-2227 ◽  
Author(s):  
Eugenia D. Teodor ◽  
Oana Ungureanu ◽  
Florentina Gatea ◽  
Gabriel L. Radu
Keyword(s):  
Medicinal Plants ◽  
Anticancer Agents ◽  
Chemical Structure ◽  
Recent Literature ◽  
Antitumor Effects ◽  
The Past ◽  
Abnormal Cells ◽  
The Individual

The tendency of using herbs extracts or natural compounds extracted from herbs for preventing or treating different illnesses, including cancer, continues to be an alternative to drug use. Many studies of plant compounds aimed at finding substances with selective cytotoxicity on abnormal cells. Phenolic compounds, as important secondary metabolites from plants, are one of them. In this review, the recent literature data from the past five years about anticancer/antitumor effect of flavonoids and tannins extracted from medicinal plants are surveyed. The cytostatic/antitumor effects of the individual compounds extracted from plants and/or of the plants' polyphenolic extracts are considered, in order to point out the most significant constituents or plants with anticancer potential. The most important results concerning these compounds and their derivatives in cancer prevention and treatment, the importance of their chemical structure, their mechanism of action in vitro and in vivo, and some bioavailability aspects are discussed.

Synthesis, Characterization and in vitro Biological Evaluation of a New Schiff Base Derived from Drug and its Complexes with Transition Metal Ions

2018 ◽  
Vol 69 (7) ◽  
pp. 1678-1681
Author(s):  
Amina Mumtaz ◽  
Tariq Mahmud ◽  
M. R. J. Elsegood ◽  
G. W. Weaver
Keyword(s):  
Schiff Base ◽  
Transition Metal ◽  
Metal Ions ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Free Ligand ◽  
Transition Metal Ions ◽  
Biological Evaluation ◽  
Pyridoxal Hydrochloride

New series of copper (II), cobalt (II), zinc (II), nickel (II), manganese (II), iron (II) complexes of a novel Schiff base were prepared by the condensation of sulphadizine and pyridoxal hydrochloride. The ligand and metal complexes were characterized by utilizing different instrumental procedures like microanalysis, thermogravimetric examination and spectroscopy. The integrated ligand and transition metal complexes were screened against various bacteria and fungus. The studies demonstrated the enhanced activity of metal complexes against reported microbes when compared with free ligand.

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