scholarly journals Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives

2018 ◽  
Vol 25 (4) ◽  
pp. 437-461 ◽  
Author(s):  
Sophie Jurgens ◽  
Fritz E. Kuhn ◽  
Angela Casini
Keyword(s):  
Anticancer Agents ◽  
Noble Metals ◽  
Organometallic Compounds ◽  
Biological Properties ◽  
Research Literature ◽  
Pincer Complexes ◽  
Special Focus ◽  
Exchange Reactions ◽  
Biological Reduction ◽  
Medicinal Properties

Background: The inherent problems accompanying chemotherapy necessitate the development of new anticancer approaches. The development of compounds that can disrupt cancerous cellular machinery by novel mechanisms, via interactions with proteins and non-canonical DNA structures (e.g. G-quadruplexes), as well as by alteration of the intracellular redox balance, is nowadays focus of intense research. In this context, organometallic compounds of the noble metals Pt and Au have become prominent experimental therapeutic agents. This review provides an overview of the Pt(II) and Au(III) cyclometalated compounds with a chelating ring containing a strong C-M σ -bond to improve the stability of the compounds with respect to ligand exchange reactions and biological reduction. Furthermore, these properties can be easily tuned by modification of either the anionic cyclometalated or the ancillary ligands. Special focus has been set to C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological mechanisms of action as anticancer agents. Methods: A structured search of both chemical and medicinal databases for peerreviewed research literature has been conducted. The quality of retrieved papers was appraised using standard tools. The synthesis as well as the chemical and biological properties of the described compounds were carefully reviewed and described. The findings were outlined using a conceptual framework. Results: In this review we included 155 papers, the majority originating from high-impact papers on the synthesis and biological modes of platinum(II) and gold(III) compounds. Among them, 17 papers were highlighted to give an introduction to the use of Pt and Au compounds with medicinal properties, mainly focussing on coordination compounds. The synthesis and medicinal properties of organometallic compounds of various metals (such as Fe, Ru, Ti) were outlined in 51 papers. These compounds included metallocenes, metallo- arenes, metallo-carbonyls, metallo-carbenes (e.g. N-heterocyclic carbenes), and alkynyl complexes. The C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum( II) (46 papers) and gold(III) (44 papers) were discussed concerning their synthesis, stability and advantages to develop therapeutic compounds. We strove to show the consistent development of C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding their synthesis and biological modes from the early beginnings to the most recent findings. Conclusion: This review supplies a profound overview of the development of organometallic compounds for medicinal purposes, setting special focus to the synthesis and stability of C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum(II) and gold(III) and their use as anticancer agents.

Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review

2020 ◽  
Vol 21 ◽  
Author(s):  
Shailaja Dombe ◽  
Pramodkumar Shirote
Keyword(s):  
Drug Delivery ◽  
Anticancer Agents ◽  
Biological Properties ◽  
The Body ◽  
Special Focus ◽  
Cancer Therapies ◽  
Nanostructured Particles ◽  
Inorganic Systems

Abstract: Cancer is the most ruinous disease globally. Natural products have impressive characteristics, such as excep-tional chemical versatility, chemical and biological properties of macromolecular specificity and less toxicity which make them good leads in finding novel drugs. The phytochemicals not only help to prevent but also treat chronic cancerous conditions. The present review attempts to put forth some selected anticancer phytochemicals that had reported omics char-acteristic and specifically suppressed cancer with in vitro and in vivo activity. Certain issues pertaining to anticancer phy-tochemicals like delivery to target site in the body and achieving controlled release in order to prevent overdoses havelong been a concern for medical researchers worldwide. The most conventional chemotherapy protocols for the treatment of cancer lead to adverse effects that limit biological efficacy and compromise patient outcomes. In order to defeat incompe-tency of current and upcoming natural anticancer agents and to attain targeted drug delivery with good efficacy and fewer side effects, there is a special focus on novel nanostructured particles and nano approaches consisting of carrier system. Recent studies have led to the discovery of mesoporous and nanoporous drug delivery mechanisms, such as inorganic or organic-based nanosponges. The metal based inorganic systems have exhibited toxicity and non-biodegradable character in vivo. As a result of problems related to inorganic systems, major shift of research from inorganic to organic nanosystems has occurred. About decades ago, researchers have developed organic nanosponges to control the limitation of drug delivery and cancer therapies. This review article discusses the development and application of nanosponges encapsulated phyto-chemicals for cancer therapy.

scholarly journals Recent Advances in the Use of the Dimerization Strategy as a Means to Increase the Biological Potential of Natural or Synthetic Molecules

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2340
Author(s):  
Alexis Paquin ◽  
Carlos Reyes-Moreno ◽  
Gervais Bérubé
Keyword(s):  
Anticancer Agents ◽  
Scientific Community ◽  
Antibacterial Agents ◽  
Biological Properties ◽  
Biologically Active ◽  
Special Focus ◽  
Reaction Sequence ◽  
Polyphenol Compounds ◽  
Recent Advances ◽  
Biological Potential

The design of C2-symmetric biologically active molecules is a subject of interest to the scientific community. It provides the possibility of discovering medicine with higher biological potential than the parent drugs. Such molecules are generally produced by classic chemistry, considering the shortness of reaction sequence and the efficacy for each step. This review describes and analyzes recent advances in the field and emphasizes selected C2-symmetric molecules (or axial symmetric molecules) made during the last 10 years. However, the description of the dimers is contextualized by prior work allowing its development, and they are categorized by their structure and/or by their properties. Hence, this review presents dimers composed of steroids, sugars, and nucleosides; known and synthetic anticancer agents; polyphenol compounds; terpenes, known and synthetic antibacterial agents; and natural products. A special focus on the anticancer potential of the dimers transpires throughout the review, notwithstanding their structure and/or primary biological properties.

scholarly journals Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1911 ◽  
Author(s):  
Odette Concepción ◽  
Julio Belmar ◽  
Alexander F. de la Torre ◽  
Francisco M. Muñiz ◽  
Mariano W. Pertino ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cd4 T Cells ◽  
Dermal Fibroblast ◽  
Colon Adenocarcinoma ◽  
Cancer Cell Lines ◽  
Biological Properties

Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2–oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.

scholarly journals Approaches towards the synthesis of 5-aminopyrazoles

2011 ◽  
Vol 7 ◽  
pp. 179-197 ◽  
Author(s):  
Ranjana Aggarwal ◽  
Vinod Kumar ◽  
Rajiv Kumar ◽  
Shiv P Singh
Keyword(s):  
Biological Properties ◽  
Synthetic Methods ◽  
Medicinal Properties ◽  
Synthetic Routes

The biological and medicinal properties of 5-aminopyrazoles have prompted enormous research aimed at developing synthetic routes to these heterocyles. This review focuses on the biological properties associated with this system. Various synthetic methods developed up to 2010 for these compounds are described, particularly those that involve the reactions of β-ketonitriles, malononitrile, alkylidenemalononitriles and their derivatives with hydrazines, as well as some novel miscellaneous methods.

Development and Advances of Drugs for Cancer Theranostics – PART-IV

2021 ◽  
Vol 21 (18) ◽  
pp. 1644-1644
Author(s):  
Lian-Shun Feng
Keyword(s):  
Drug Discovery ◽  
Side Effects ◽  
Anticancer Activity ◽  
Anticancer Drug ◽  
Anticancer Agents ◽  
Drug Repurposing ◽  
Biological Properties ◽  
Drug Candidates ◽  
Pharmacokinetic Profiles ◽  
Hybrid Molecules

Cancer, a highly heterogeneous disease at intra/inter patient levels, is one of the most serious threats to human health across the world [1, 2]. Notwithstanding the noteworthy advances in its treat-ment, the morbidity and mortality of cancer are projected to grow for a long period, and the global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020 [3]. Accordingly, there is a constant need to explore novel anticancer agents. <p> There are several strategies to discover novel anticancer candidates: (1) new lead hits or candidates from natural resources [4] whichexhibit various biological properties and are a rich source of com-pounds in drug discovery due to the structural and mechanistic diversity, and more than 60% anti-cancer agents can be traced to a natural product; (2) Molecular hybridization is one of the most prom-ising strategies for the discovery of novel anticancer drug candidates since hybrid molecules have the potential to bind multiple targets or to enhance the effect through acting with another bio-target or to counterbalance the side effects caused by the other part of the hybrid [5]; (3) Dimerization is a useful tool to develop novel anticancer drug candidates with enhanced biological activity, reduced side effects and improved pharmacokinetic profiles [6]; (4) Drug repurposing strategy is is an attractive strategy and has been approved, along with non-anticancer macrolide drugs for the treatment of cancer, for anticancer drug discovery since toxicity and pharmacokinetic profiles have already been estab-lished [7]. <p> Heterocycles coumarin, β-lactone, macrolide and triazole are useful anticancer pharmacophores since their derivatives could exert the anticancer activity through diverse mechanisms, inclusive of inhibition of aromatase, carbonic anhydrase, ki-nase, P-glycoprotein, sulfatase, telomerase, vascular endothelial growth factor receptor 2 and tubulin [8-11]. In particular, nat-ural-derived coumarin, β-lactone and macrolide derivatives are important sources of new anticancer lead hits/candidates; mac-rolide repurposed drugs can circumvent high cost and long-time associated with traditional drug discovery strategies; couma-rin, β-lactone and macrolide hybrids as well as bis-triazole compounds have the potential to enhance the anticancer activity, overcome drug resistance, reduce the side effects and improve pharmacokinetic profiles.

scholarly journals Ferrocenes as Potential Anticancer Drugs: Determination of the Mechanism of Action

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 16
Author(s):  
Hrstka ◽  
Skoupilová ◽  
Bartošík ◽  
Sommerová ◽  
Karban ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Organometallic Compounds ◽  
Differential Pulse ◽  
Vital Role ◽  
Intracellular Accumulation ◽  
Ferrocene Derivatives

Chemotherapy is an essential treatment that still plays a vital role in cancer treatment worldwide. The ferrocene derivatives of the general formula [Fe{(η5‑C5H4CH2(p‑C6H4)CH2(N‑het)}2] bearing modified six and five membered N-heterocycles were tested in vitro for their cytotoxic properties against ovarian cancer cell lines A2780 and SK-OV-3. These ferrocene complexes displayed cytotoxicity in low micromolar concentrations against both cell lines. To study cellular uptake of particular ferrocenes into tumor cells, we used differential pulse voltammetry and ICP-MS. We confirmed the crucial role of transferrin receptors in the process of intracellular accumulation of these ferrocenes. Interestingly, the rate of intracellular accumulation of particular ferrocenes clearly mirrored the cytotoxicity of these organometallic compounds. Deeper investigation of the mechanism by which ferrocenes kill tumor cells revealed induction of apoptosis associated with significant increase of reactive oxygen species. In conclusion, our screening identified several ferrocene derivatives exerting promising cytostatic activity in vitro. Further investigation led to the identification of the mechanism of action of these potential anticancer agents, which represents an important milestone in preclinical anticancer drug discovery programs. This work was supported by the project MEYS-NPS I-LO1413, MH CZ-DRO (MMCI, 00209805) and Czech Science Foundation project 17-05838S.

scholarly journals Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

2020 ◽  
Vol 21 (22) ◽  
pp. 8692
Author(s):  
Alessandra Benassi ◽  
Filippo Doria ◽  
Valentina Pirota
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Properties ◽  
Aromatic Rings ◽  
Antitumor Effects ◽  
Comprehensive Overview ◽  
Biological Targets ◽  
Structural Modifications ◽  
Starting Point ◽  
Oxadiazole Derivatives

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

scholarly journals Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

2019 ◽  
Vol 12 (4) ◽  
pp. 146 ◽  
Author(s):  
Claudia Riccardi ◽  
Domenica Musumeci ◽  
Marco Trifuoggi ◽  
Carlo Irace ◽  
Luigi Paduano ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Biomedical Applications ◽  
Special Focus ◽  
Anticancer Properties ◽  
Pharmacokinetic Properties ◽  
Pharmacological Potential

The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications.

scholarly journals Hovenia dulcis Thumberg: Phytochemistry, Pharmacology, Toxicology and Regulatory Framework for Its Use in the European Union

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 903
Author(s):  
Gianluca Sferrazza ◽  
Gloria Brusotti ◽  
Manuela Zonfrillo ◽  
Caterina Temporini ◽  
Sara Tengattini ◽  
...  
Keyword(s):  
European Union ◽  
Herbal Remedy ◽  
Biological Activities ◽  
Water Extract ◽  
Biological Properties ◽  
Hot Water ◽  
Special Focus ◽  
Root Bark ◽  
The European Union ◽  
Hovenia Dulcis

Hovenia dulcis Thunberg is an herbal plant, belonging to the Rhamnaceae family, widespread in west Asia, USA, Australia and New Zealand, but still almost unknown in Western countries. H. dulcis has been described to possess several pharmacological properties, such as antidiabetic, anticancer, antioxidant, anti-inflammatory and hepatoprotective, especially in the hangover treatment, validating its use as an herbal remedy in the Chinese Traditional Medicine. These biological properties are related to a variety of secondary metabolites synthesized by the different plant parts. Root, bark and leaves are rich of dammarane-type triterpene saponins; dihydrokaempferol, quercetin, 3,3′,5′,5,7-pentahydroflavone and dihydromyricetin are flavonoids isolated from the seeds; fruits contain mainly dihydroflavonols, such as dihydromyricetin (or ampelopsin) and hovenodulinol, and flavonols such as myricetin and gallocatechin; alkaloids were found in root, barks (frangulanin) and seeds (perlolyrin), and organic acids (vanillic and ferulic) in hot water extract from seeds. Finally, peduncles have plenty of polysaccharides which justify the use as a food supplement. The aim of this work is to review the whole scientific production, with special focus on the last decade, in order to update phytochemistry, biological activities, nutritional properties, toxicological aspect and regulatory classification of H. dulcis extracts for its use in the European Union.

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