Ferrocene-Based Drugs, Delivery Nanomaterials and Fenton Mechanism: State of the Art, Recent Developments and Prospects

Ferrocene has been the most used organometallic moiety introduced in organic and bioinorganic drugs to cure cancers and various other diseases. Following several pioneering studies, two real breakthroughs occurred in 1996 and 1997. In 1996, Jaouen et al. reported ferrocifens, ferrocene analogs of tamoxifen, the chemotherapeutic for hormone-dependent breast cancer. Several ferrocifens are now in preclinical evaluation. Independently, in 1997, ferroquine, an analog of the antimalarial drug chloroquine upon the introduction of a ferrocenyl substituent in the carbon chain, was reported by the Biot-Brocard group and found to be active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Ferroquine, in combination with artefenomel, completed phase IIb clinical evaluation in 2019. More than 1000 studies have been published on ferrocenyl-containing pharmacophores against infectious diseases, including parasitic, bacterial, fungal, and viral infections, but the relationship between structure and biological activity has been scarcely demonstrated, unlike for ferrocifens and ferroquines. In a majority of ferrocene-containing drugs, however, the production of reactive oxygen species (ROS), in particular the OH. radical, produced by Fenton catalysis, plays a key role and is scrutinized in this mini-review, together with the supramolecular approach utilizing drug delivery nanosystems, such as micelles, metal–organic frameworks (MOFs), polymers, and dendrimers

A One-Pot Synthesis of a 243-Allyl Dendrimer under Ambient Conditions

Hydrosilylation of a nonaallyl dendritic core using HSi(Me)2Cl followed by reaction with a phenolate dendronic brick bearing three allyl groups, followed by repetition of this sequence of reactions twice, allows a one-pot synthesis of a 243-allyl dendrimer under ambient conditions

Interlocked Systems In Nanomedicine.

The concept of Nanomedicine emerged along with the new millennium, and it is expected to provide solutions to some of modern medicine's unsolved problems. Nanomedicine offers new hopes in several critical areas such as cancer treatment, viral and bacterial infections, medical imaging, tissue regeneration, and theranostics. To explore all these applications, a wide variety of nanomaterials have been developed which include liposomes, dendrimers, nanohydrogels and polymeric, metallic and inorganic nanoparticles. Recently, interlocked systems, namely rotaxanes and catenanes, have been incorporated into some of these chemical platforms in an attempt to improve their performance. This review focus on the nanomedicine applications of nanomaterials containing interlocked structures. The introduction gives an overview on the significance of interdisciplinary science in the progress of the nanomedicine field, and it explains the evolution of interlocked molecules until their application in nanomedicine. The following sections are organized by the type of interlocked structure, and it comprises details of the in vitro and/or in vivo experiments involving each material: rotaxanes as imaging agents, rotaxanes as cytotoxic agents, rotaxanes as peptide transporters, mechanized silica nanoparticles as stimuli responsive drug delivery systems, and polyrotaxanes as drug and gene delivery systems.151236-125

A Career in Catalysis: Didier Astruc

International audienceWe are honored to reflect on and highlight in this Account Didier Astrues achievements in various aspects of catalysis stretching from his concept and design of organoiron electron reservoir complexes and application to redox and electrocatalysis to his dendritic constructions leading to their use in dendritic catalysis, supramolecular nanocatalysis, and energyrelated catalysis. It is at the end of the 70s that Didier Astruc isolated the first stable, well-characterized 19-electron sandwich complex as an electron reservoir and disclosed their catalytic applications. At the same time, he developed an original system of arene polyfunctionalization to star-shaped molecules and dendrimers that he then decorated with catalysts for oxidation, electrocatalysis, polymerization by ROMP, and other olefin metathesis reactions. After disclosure by his group of click metallodendrimers during the first decade of this century, he used them as templates for synthesis of well-defined ultrasmall metal nanoparticles extremely active in catalysis for olefin hydrogenation and C-C bond formation using extremely low catalytic amounts. During the last 15 years, Didier Astruc designed dendritic micellar nanoreactors for molecular, ionic, and nanoparticle catalysis; autocatalysis; and nanozyme catalysis. Recently, his interest focused inter alia on nanocatalyzed hydrogen (H-2) production with very efficient endo- and exoreceptors and CO2 fixation, a field of sustainable energy in which he and his group are currently very active

Biodegradable and ph-responsive acetalated dextran (Ac-Dex) nanoparticles for nir imaging and controlled delivery of a platinum-based prodrug into cancer cells

Nanoparticles (NPs) based on the biodegradable acetalated dextran polymer (Ac-Dex) were used for near-infrared (NIR) imaging and controlled delivery of a PtIV prodrug into cancer cells. The Ac-Dex NPs loaded with the hydrophobic PtIV prodrug 3 (PtIV/Ac-Dex NPs) and with the novel hydrophobic NIR-fluorescent dye 9 (NIR-dye 9/Ac-Dex NPs), as well as Ac-Dex NPs coloaded with both compounds (coloaded Ac-Dex NPs), were assembled using a single oil-in-water nanoemulsion method. Dynamic light scattering measurements and scanning electron microscopy images showed that the resulting Ac-Dex NPs are spherical with an average diameter of 100 nm, which is suitable for accumulation in tumors via the enhanced permeation and retention effect. The new nanosystems exhibited high drug-loading capability, high encapsulation efficiency, high stability in physiological conditions, and pH responsiveness. Drug-release studies clearly showed that the PtIV prodrug 3 release from Ac-Dex NPs was negligible at pH 7.4, whereas at pH 5.5, this compound was completely released with a controlled rate. Confocal laser scanning microscopy unambiguously showed that the NIR-dye 9/Ac-Dex NPs were efficiently taken up by MCF-7 cells, and cytotoxicity assays against several cell lines showed no significant toxicity of blank Ac-Dex NPs up to 1 mg mL–1. The IC50 values obtained for the PtIV prodrug encapsulated in Ac-Dex NPs were much lower when compared with the IC50 values obtained for the free PtIV complex and cisplatin in all cell lines tested. Overall, our results demonstrate, for the first time, that Ac-Dex NPs constitute a promising drug delivery platform for cancer therapy16520832094CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP573913/2008-0Não tem2018/02093-0; 2017/06146-8; 2017/24488-3; 08/57906-3The authors gratefully acknowledge Sao Paulo Research Foundation—FAPESP (grant #2018/02093-0 for C.O.; fellowship #2017/06146-8 for C.B.B.; scholarship #2017/24488-3 for G.P.) and Coordination for the Improvement of Higher Education Personnel—CAPES (Ph.D. scholarship for T.B.B.) for the financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior—Brasil (CAPES), finance code 001. We also thank the access to equipment and assistance provided by the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the State University of Campinas; INFABIC is cofunded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) (08/57906-3) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) (573913/2008-0

Cross olefin metathesis for the selective functionalization, ferrocenylation, and solubilisation in water of olefin-terminated dendrimers, polymers, and gold nanoparticles and for a divergent dendrimer construction

Olefin cross metathesis was used to efficiently functionalize, polyolefin dendrimers, polymers, and gold nanoparticles using the second-generation Grubbs catalyst. In these structures, the tethers were lengthened to prevent the facile cross metathesis that otherwise predominates in polyolefin dendrimers having short tethers. This synthetic strategy allows the one-step access to polyacid, polyester, and polyferrocenyl structures from polyolefins. Cross metathesis is also used to efficiently achieve an iterative divergent dendritic construction. All the cross metathesis reactions were monitored by H-1 NMR showing the chemio-, regio-, and stereoselectivity. MALDI-TOF mass spectrometry was a very useful technique to confirm the efficiency of this synthetic strateg

Synthesis of nitrogen-containing goniothalamin analogues with higher cytotoxic activity and selectivity against cancer cells

Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 mu m) and PC3 (0.3 mu m) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50=0.8 mu m), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines141514031417CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2013/07607-8; 2018/02093-0134836/2016-

Anti-inflammatory activity of polyamide dendrimers bearing bile acid termini synthesized via SPAAC

Inflammation is a general pathomechanism associated with numerous diseases of global impact such as many cancers, metabolic disorders, and neurodegenerative and autoimmune diseases. The development of drugs that can treat chronic inflammation, in an effective way and that are well tolerated by the patients, is an active research area that pursues the treatment for hundreds of diseases. Dendrimers recently appeared as a convenient starting point for the design of anti-inflammatory drugs due to its nanosize, well-defined branched structure, multivalency, and versatility. In this work, polyamide dendrimers with 1 -> 3 connectivity were synthesized and functionalized with three types of bile acids (BAs): cholic acid (CA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). Functionalization was carried out through strain-promoted alkyne-azide cycloaddition (SPAAC) between an azide dendrimer and cyclooctyne derivatives of bile acids. The cell viability and the anti-inflammatory potential of the bile acid dendrimers were evaluated in vitro and compared with those of the pure BAs. The bile acid dendrimers and pure BAs did not show significant cytotoxicity at the concentrations tested (0.78-5.00 x 10(4) nM) against THP-1 cells. Chenodeoxycholic acid (CDCA) and the corresponding dendrimer dendri-(CDCA)(18) (polyamide dendrimer bearing 18 CDCA moieties) presented the highest anti-inflammatory activity, showing LPS-induced IL-8 release inhibition of 45.3% at 0.78 nM CDCA and 35.5% at 0.43 nM dendri-(CDCA)(18)2111CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível SuperiorCNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo57417991; 91674518307403/2018-12018/02093-0; 15/04929-