31,576 research outputs found
Palladium organometallic compounds bearing N-Heterocyclic Carbene ligands as promising anticancer agents
No full textDespite 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
Thomas Grisell letter to Thomas Rotch, 2nd mo 19th 1823
No full textThomas Grisell's letter reached the Rotch household several months before the unexpected death of Thomas Rotch in August, 1823. This is the last letter of the series and presumably the author learned of his friend's death before another letter was penned. 7.95" x 10" (20.2 by 25.5 cm
La nascita di un corpus di scolii a Sofocle: il caso del Parmensis 3176 (De Rossi 8) e del Marc. Gr. IX 27
No full textThis paper deals with the Renaissance tradition of the scholia on Sophocles, both ancient and Byzantine. The focus will be on the manuscript Parma, Biblioteca Palatina, Parm. 3176 which hands down a peculiar set of scholia on Sophocles whereby ancient and Byzantine scholia written by Manuel Moschopoulos, Thomas Magister and Demetrius Triclinius are combined. The aim is threefold: (1) to clarify the principles according to which the Parma set of scholia was put together; (2) to present the manuscript Venezia, Biblioteca Nazionale Marciana, Marc. gr. ix 27 which I will show to be the only surviving complete apograph of the Parma recension; (3) to shed some light on the historical milieu of the manuscripts, with special regard to the vexed question of the missed opportunity of publishing the first print edition of the scholia to accompany the editio princeps of the tragedies of Sophocles (Venice 1502)
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
Failed Censures: Ecclesiastical Regulation of Women’s Clothing in Late Medieval Italy
No full textChurchmen in the late thirteenth and early fourteenth centuries tried to regulate the costume of Italian women. These efforts failed, and regulation was largely left thereafter to civic authorities.The published version was published as Chapter 3 in Medieval Clothing and Textiles 5Izbicki, Thomas M. (2009), "Failed Censures: Ecclesiastical Regulation of Women’s Clothing in Late Medieval Italy" in Netherton, Robin and Owen-Crocker, Gale R., eds., Medieval Clothing and Textiles 5 (Boydell Press), 37-53ISBN: 9781843834519 (published book)Peer reviewe
Western medieval legal manuscripts in the collections of the University of Pennsylvania
No full textWestern legal manuscripts of the Middle Ages in North American collections are among the least known to scholars. The University of Pennsylvania has a rich collection of these texts, several of which were in the collection of the historian Henry Charles Lea. Included are works of civil law and canon law, as well as collections of papal letters and guides to pastoral care. The descriptions of most of these manuscripts in the catalog of Norman P. Zacour and Rudolf Hirsch are perfunctory, sometimes erring or omitting valuable information. Other manuscripts were added in recent years in the Lawrence J. Schoenberg Collection. Much of this material is being added to the Franklin online catalog of the University’s libraries, but researchers frequently do not search these digital resources. This article provides more complete guidance to the University’s medieval legal manuscripts than any of the existing catalogs offers, whether in print or online. It also provides updated bibliographic information in print or online. Every manuscript has been examined by the author in situ. Among the important works represented in the collection is the Panormia (a work of canon law often attributed to Ivo of Chartres). Authors present include the curialist Thomas of Capua, canonists Petrus de Braco, William of Pagula, Bernardus Raimundi, Adam of Aldersbach, Raymond of Peñafort, and civil lawyers Baldus de Ubaldis, and Bartolus de Saxoferrato. Three of these manuscripts were owned in the past by Sir Thomas Phillipps
Forbidden Colors in the Regulation of Clerical Dress from the Fourth Lateran Council (1215) to the Time of Nicholas of Cusa (d. 1464)
No full textMedieval canon law attempted to distinguish clergy from the laity by restricting their dress choices. The article focuses on prohibition of wearing red or green on the street. Both colors were identified with the nobility.The published version was published as Chapter 7 in Medieval Clothing and Textiles 1Izbicki, Thomas M. (2005), "Forbidden Colors in the Regulation of Clerical Dress from the Fourth Lateran Council (1215) to the Time of Nicholas of Cusa (d. 1464)" in Netherton, Robin and Owen-Crocker, Gale R., eds., Medieval Clothing and Textiles 1 (Boydell Press),105-114ISBN: 9781843831235 (published book
Thomas Crutchfield account book, 1848-1861
No full textA book containing business accounts, including details about travel expenses and the purchase and sale of lumber as well as other goods and services. The author also catalogs personal spending, the dates and pricing of properties offered for rent, and the purchase and leasing of enslaved people. Many entries are consistent with the business activities of Thomas Crutchfield Sr., who died in 1850. Someone continued to make entries in the book for activities dated up to 1861
Thomas Crutchfield account book, 1848-1861
No full textA book containing business accounts, including details about travel expenses and the purchase and sale of lumber as well as other goods and services. The author also catalogs personal spending, the dates and pricing of properties offered for rent, and the purchase and leasing of enslaved people. Many entries are consistent with the business activities of Thomas Crutchfield Sr., who died in 1850. Someone continued to make entries in the book for activities dated up to 1861
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