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 Total syntheses of the archazolids: an emerging class of novel anticancer drugs

2017 ◽  
Vol 13 ◽  
pp. 1085-1098 ◽  
Author(s):  
Stephan Scheeff ◽  
Dirk Menche
Keyword(s):  
Total Synthesis ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Preclinical Development ◽  
Total Syntheses ◽  
Atpase Inhibitors ◽  
Anticancer Target

V-ATPase has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with the archazolids, complex polyketide macrolides which present the most potent V-ATPase inhibitors known to date, rendering these macrolides important lead structures for the development of novel anticancer agents. The limited natural supply of these metabolites from their myxobacterial source renders total synthesis of vital importance for the further preclinical development. This review describes in detail the various tactics and strategies employed so far in archazolid syntheses that culminated in three total syntheses and discusses the future synthetic challenges that have to be addressed.

scholarly journals The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1212
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Drug Toxicity ◽  
Multi Drug Resistance ◽  
Drug Bioavailability

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo.

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 In Vitro and In Vivo evaluation of novel anticancer agents in triple negative Breast Cancer Models

2013 ◽  
Vol 24 (1A) ◽  
pp. 104-111 ◽  
Author(s):  
KiTani Parker Johnson ◽  
Letitia A. Yearby ◽  
Diana Stoute ◽  
Matthew E. Burow ◽  
Lyndsay V. Rhodes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Cancer Models

scholarly journals Preclinical Development of Mahanine-Enriched Fraction from Indian Spice Murraya koenigii for the Management of Cancer: Efficacy, Temperature/pH stability, Pharmacokinetics, Acute and Chronic Toxicity (14-180 Days) Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Eswara Murali Satyavarapu ◽  
Prasun Kumar Sinha ◽  
Chitra Mandal
Keyword(s):  
Breast Cancer ◽  
Chronic Toxicity ◽  
Hematological Parameters ◽  
Clinical Signs ◽  
Murraya Koenigii ◽  
Preclinical Development ◽  
Dapi Staining ◽  
Wide Range

Murraya koenigii is well documented in the Indian ancient medical text “Charaka Samhita.” The carbazole alkaloid “mahanine” from this plant exhibited anticancer activity against several cancers. Here, we have taken a comprehensive study to standardize the method for the preparation of a mahanine-enriched fraction (MEF) with the highest yield and defined markers. Our optimized method produced MEF having the highest amount of mahanine, a major marker, with excellent in vitro antiproliferative activity against ovarian and breast cancer cells as evidenced by decreased cell viability by MTT assay. Moreover, it exhibited condensed and fragmented nuclei by DAPI staining and increased annexin V-/PI-stained cells after MEF treatment, indicating apoptosis. It also exhibited good efficacy in ovarian and breast cancer syngeneic mice models, with an ED50 of 300 mg/kg body weight (BW). MEF is stable up to 40°C for ≥3 months. Its biological activity remains unchanged at a wide range of pH (1-10) for up to ~3 hours, indicating a safe oral route of administration. Additionally, the comparative pharmacokinetics of MEF and mahanine in rats showed a 31% higher bioavailability of mahanine in MEF-fed rats compared to rats fed with mahanine alone. Furthermore, mice fed with MEF at 5000 mg/kg BW single dose, 300-1500 mg/kg BW/day for 14 days, and 300 mg/kg BW/day for 28, 90, and 180 days for subacute, subchronic, chronic studies, respectively, did not show any significant clinical signs of toxicity, behavioral changes, mortality, organ weights, serum biochemistry, and hematological parameters indicating no/minimum toxicity for up to 180 days. To the best of our knowledge, this is the first report showing the pH/temperature stability and chronic toxicity studies of MEF along with in vivo efficacy against breast cancer. Taken together, our study will enhance the commercial value of this highly potential medicinal plant and will be helpful as a reference material for its clinical development.

scholarly journals Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 416 ◽  
Author(s):  
Abd Amr ◽  
Elsayed Elsayed ◽  
Mohamed Al-Omar ◽  
Hanan Badr Eldin ◽  
Eman Nossier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
Docking Study ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Elemental Analyses

A series of estrone derivatives 3–8 was designed and synthesized using estrone arylmethylenes 2a,b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.

scholarly journals Alkaloids Isolated from Natural Herbs as the Anticancer Agents

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jin-Jian Lu ◽  
Jiao-Lin Bao ◽  
Xiu-Ping Chen ◽  
Min Huang ◽  
Yi-Tao Wang
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Chemical Compounds ◽  
Mechanisms Of Action ◽  
Anticancer Properties ◽  
Important Chemical

Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers bothin vitroandin vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

scholarly journals Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Amol Shindikar ◽  
Akshita Singh ◽  
Malcolm Nobre ◽  
Saurabh Kirolikar
Keyword(s):  
Breast Cancer ◽  
Effective Treatment ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Genetic Changes ◽  
Anticancer Properties ◽  
Natural Remedies

Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties.In vitroandin vivostudies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems.

scholarly journals Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1559
Author(s):  
Elena Domínguez-Jurado ◽  
Francisco J. Cimas ◽  
José Antonio Castro-Osma ◽  
Alberto Juan ◽  
Agustín Lara-Sánchez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Acquired Resistance ◽  
In Vitro Cytotoxicity ◽  
Clinical Development ◽  
Rational Drug Design ◽  
Preclinical Development ◽  
Cancer Subtypes ◽  
Ruthenium Compounds

Despite some limitations such as long-term side effects or the potential presence of intrinsic or acquired resistance, platinum compounds are key therapeutic components for the treatment of several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they have a more favorable toxicity profile and represent an ideal template for both, high-throughput and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium compounds in the treatment of breast cancer, we carried out chemical modifications in the structure of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo toxicity was also assessed. The results obtained in this article might pave the way for the clinical development of these compounds in breast cancer therapy.

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