1,721,073 research outputs found
Palladium organometallic compounds bearing N-Heterocyclic Carbene ligands as promising anticancer agents
Full text linkDespite the appearance in the market of platinum compounds with minor side effects than cisplatin (i.e. carboplatin and oxaliplatin), they did not solve the ineffectiveness on some types of tumors, having the same mechanism of action proposed for cisplatin (DNA platination).
For this reason, many research groups have focused their attention on the synthesis and determination of the anticancer properties of compounds with metals different from platinum.
Among the most investigated metals there are certainly ruthenium and gold and, only recently, palladium.
The latter, despite belonging to the same group of platinum, has some rather different features:
•Better water solubility of its complexes.
•Structure-activity relationships and mechanisms of action generally different from platinum compounds.
However, the fast dissociation pattern of palladium complexes compared to platinum represents a problem since the speciation, which heavily affects the biological activity and the pharmacokinetic properties, could be increased. To remedy this contraindication the most direct option is the introduction of ligands firmly anchored to the metal such as N-Heterocylic Carbenes (NHCs), which are known to give strong s-bonds with most of the transition metals.
Moreover, several NHC-palladium complexes have already exhibited an interesting cytotoxic activity in vitro and tumour growth suppression even in vivo.
In this PhD thesis, the synthesis and characterization of new palladium compounds stabilized by different types of N-Heterocyclic Carbenes and important organometallic fragments such as h3-allyl-Pd(II), palladacyclopentadienyl and h2-olefin-Pd(0) will be exposed.
The reactivity and the importance in many catalytic processes of the fragments reported in Fig. A1 are well known, on the contrary, their biological activity is almost unexplored.
Starting from these premises, it was decided to test the synthesized compounds toward different tumor lines, particularly on ovarian carcinoma, and human fibroblasts (healthy cells).
From the antiproliferative activity data collected for about one hundred compounds, emerges that, regardless of the nature of the selected carbene ligand, the most active compounds bear the allyl fragment.
For these species the evaluation of their activity in vivo and experiments aimed at identify the primary biological target, in order to propose the possible mechanism of action, are planned.
A class of compounds generally slightly less active than that containing the allyl residue is represented by the palladacyclopentadienyl complexes and their derivatives. Nevertheless, for some of the synthesized compounds, an excellent antiproliferative and proapoptotic activity has been shown on ovarian cancer cell lines (CisPt sensitive and CisPt resistance), accompanied by a poor activity against normal cells.
For the compound 40a a thorough investigation on the main biological target, which was found to be DNA, and on the degree of uptake in tumor cells was also carried out.
Due to the high stability imparted by the palladaciclopentadienyl fragment and the chelatig biscarbene ligand, this compound does not undergo substitution reactions when reacted with reduced glutathione (GSH), which is a potential coordinating species present in abundance in the biological environment.
It is therefore reasonable to suppose that the interaction with the DNA occurs through non-covalent interactions with the polynucleotide chain.
Finally, the class of compounds decidedly less active than those described so far is represented by the Pd (0) derivatives stabilized by olefinic ligands. For these complexes the antiproliferative and proapoptotic activity was evaluated only in ovarian carcinoma lines, observing only in very few cases IC50 values comparable to those of cisplatin
Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads
No full textThis review highlights significant advancements in antibody–drug conjugates (ADCs)
equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering
a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Liposomal Formulations of Metallodrugs for Cancer Therapy
Full text linkThe search for new antineoplastic agents is imperative, as cancer remains one of the most
preeminent causes of death worldwide. Since the discovery of the therapeutic potential of cisplatin,
the study of metallodrugs in cancer chemotherapy acquired increasing interest. Starting from cisplatin
derivatives, such as oxaliplatin and carboplatin, in the last years, different compounds were explored,
employing different metal centers such as iron, ruthenium, gold, and palladium. Nonetheless,
metallodrugs face several drawbacks, such as low water solubility, rapid clearance, and possible side
toxicity. Encapsulation has emerged as a promising strategy to overcome these issues, providing both
improved biocompatibility and protection of the payload from possible degradation in the biological
environment. In this respect, liposomes, which are spherical vesicles characterized by an aqueous
core surrounded by lipid bilayers, have proven to be ideal candidates due to their versatility. In
fact, they can encapsulate both hydrophilic and hydrophobic drugs, are biocompatible, and their
properties can be tuned to improve the selective delivery to tumour sites exploiting both passive
and active targeting. In this review, we report the most recent findings on liposomal formulations of
metallodrugs, with a focus on encapsulation techniques and the obtained biological results
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Mannose‐Inspired Mesoionic Carbenes: Building Antitumor Palladium(II) Allyl Complexes
No full textThe synthesis and anticancer evaluation of palladium(II) com-plexes bearing mannose-conjugated mesoionic carbenes andtheir triazolium precursors (triazolium palladates) is reported.Ligand precursors are easily obtained via copper-catalyzedazide–alkyne cycloaddition. Palladium allyl carbene complexesare prepared extending the weak base route protocol to triazo-lium salts by reacting the metal precursor and azolium salts withpotassium carbonate as the base in acetonitrile and under mildconditions. Additionally, triazolium allyl palladates are isolated,which represent the first examples of triazolium palladate com-plexes described in the literature. In vitro tests on a panel of can-cer cell lines (A2780, A2780cis, DLD-1) reveal better or comparablecytotoxicity to cisplatin. The majority of complexes exhibit lowcytotoxicity (>100 μM) toward MRC-5 and FT-190 nontumoral celllines demonstrating remarkable in vitro selectivity
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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