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In this work, we report the identification of novel bromodomain‐containing protein 9 (BRD9) binders through a virtual screening based on our developed 3D structure‐based pharmacophore model. The in silico workflow here described led to the identification of a promising initial hit (1) featuring the 1‐ethyl‐1H‐pyrazolo[3,4‐b]pyridine motif which represented an unexplored chemotype for the development of a new class of BRD9 ligands. The encouraging biophysical results achieved for compound 1 prompted us to explore further tailored structural modification around the C‐4 and C‐6 positions of the central core. Hence, the design and synthesis of a set of 19 derivatives (2–20) were performed to extensively investigate the chemical space of BRD9 binding site. Among them, four compounds (5, 11, 12, and 19) stood out in biophysical assays as new valuable BRD9 ligands featuring IC50 values in the low‐micromolar range. Noteworthy, a promising antiproliferative activity was detected in vitro for compound 5 on HeLa and A375 cancer cell line. The successful combination and application of in silico tools, chemical synthesis, and biological assays allowed to identify novel BRD9 binders and to expand the arsenal of promising chemical entities amenable to the recognition of this important epigenetic target. [ABSTRACT FROM AUTHOR]

This work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5‐nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)]± or [Au(HTSC)2]±, and/or dimeric species. Neutral [{Au(TSC)}2] species were obtained from one of the compounds in dichlomethane/n‐hexane solution and characterized by X‐ray crystallography revealing a Au−Au bond, and deprotonated thiosemicarbazone (TSC). The cytotoxicity of the gold compounds and thiosemicarbazone ligands was evaluated against selected cancer cell lines and compared to that of Auranofin. Studies of the most stable, cytotoxic, and selective compound on a renal cancer cell line (Caki‐1) demonstrated its relevant antimigratory and anti‐angiogenic properties, and preferential accumulation in the cell nuclei. Its mode of action seems to involve interaction with DNA, and subsequent cell death via apoptosis. [ABSTRACT FROM AUTHOR]

A series of four binuclear complexes of general formula [(C^C)Au(Cl)(L^L)(Cl)Au(C^C)], where C^C is 4,4'‐diterbutylbiphenyl and L^L is either a bridging diphosphine or 4,4'‐bipyridine, are synthetized with 52 to 72 % yield and structurally characterized by X‐ray diffraction. The use of the chelating 1,2‐diphenylphosphinoethane ligand in a 1 : 2 (P^P):Au stoichiometry leads to the near quantitative formation of a gold double‐complex salt of general formula [(C^C)Au(P^P)][(C^C^)AuCl2]. The compounds display long‐lived yellow‐green phosphorescence with λem in the range of 525 to 585 nm in the solid state with photoluminescence quantum yields (PLQY) up to 10 %. These AuIII complexes are tested for their antiproliferative activity against lung adenocarcinoma cells A549 and results show that compounds 2 and 5 are the most promising candidates. The digold salt 5 shows anticancer activity between 66 and 200 nM on the tested cancer cell lines, whereas derivative 2 displays concentration values required to reduce by 50 % the cell viability (IC50) between 7 and 11 μM. Reactivity studies of compound 5 reveal that the [(C^C)Au(P^P)]+ cation is stable in the presence of relevant biomolecules including glutathione suggesting a structural mechanism of action. [ABSTRACT FROM AUTHOR]

AC1‐004 is a potent inhibitor of the hypoxia‐inducible factor alpha (HIF‐1α) pathway, essential for tumour growth, angiogenesis and metastasis. We modelled a series of gold(I) complexes on AC1‐004, retaining its 5‐carboalkoxybenzimidazole as an NHC ligand while replacing its 2‐aryloxymethyl residue with modified thiolato gold(I) fragments. The intention was to augment a potential HIF‐1α inhibition by conducive effects typical of NHC gold complexes, such as an inhibition of tumoural thioredoxin reductase (TrxR), an increase in reactive oxygen species (ROS), and cytotoxic and antiangiogenic effects. We report on the synthesis and biological effects of twelve such N,N'‐dialkylbenzimidazol‐2‐ylidene gold(I) complexes, obtained in average yields of 65 % for the thiophenolato and 45 % for the novel 4‐(adamant‐2‐yl)benzenethiol complexes. The structure of one complex was validated via single‐crystal X‐ray diffraction. Structure‐activity relationships (SAR) were derived by variation of the N‐substituents (Me, Et, iPr, pentyl, Bn) and the thiolato ligand. Their cytotoxicity against various human cancer cell lines of different entities reached IC50 values in the single‐digit micromolar range. The complexes were also assayed for the induction of tumour cell apoptosis (activation of caspase‐3/7), TrxR inhibition and antiangiogenic effects in zebrafish. Cyclopropene‐bearing congeners were employed in click reactions to examine the subcellular accumulation of the complexes. [ABSTRACT FROM AUTHOR]

Biocompatible hydroxylated boron nitride nanosheets were effectively loaded with indocyanine green and doxorubicin using successive assembly. The indocyanine green/doxorubicin‐loaded hydroxyl boron nitride nanosheets (ICG/DOX@OH‐BNNS) integrated photothermal therapy and chemotherapy into a single nano vehicle. It had been confirmed that ICG/DOX@OH‐BNNS could produce reactive oxygen species and exhibit excellent photothermal effects and light‐triggered faster DOX release with NIR laser irradiation. On the other hand, the fluorescence of DOX in ICG/DOX@OH‐BNNS was also used for visualizing subcellular location. Compared with individual chemotherapy and photothermal therapy, the combined treatment of ICG/DOX@OH‐BNNS could synergistically induce the apoptosis and death of A549 cells and suppress S180 tumor growth in vivo. [ABSTRACT FROM AUTHOR]

This work reports the preparation and characterization of an A2B corrole 5,15‐bis(perfluorophenyl)‐10‐(4‐carboxyphenyl)corrole and its gallium(III) and phosphorus(V) complexes. Their in‐vitro photodynamic anticancer activities against A549, MDA‐MB‐231, B16, HepG2, and Hela cell lines were also investigated. Among three compounds, phosphorus(V) complexexhibits the best photostability, highest fluorescence quantum yields (ΦF=0.138), and the highest singlet‐oxygen quantum yields (ΦΔ=0.87). Also, the phosphorus(V) complex exhibits the best photodynamic antitumor activity against MDA‐MB‐231 cells with a low IC50 (0.08 μM) upon light irradiation at 625±2 nm, which is much lower than commercial PDT drug Temoporfin (0.1 μM) at the same conditions. The cellular localization assay confirmed that the phosphorus(V) complexis mainly distributed in the cytoplasm and have a good ability to produce reactive oxygen species (ROS) under light illumination, which would further cause oxidative damage to tumor cells and finally result in the apoptosis. After PDT treatment, phosphorus(V) complex may cause tumor cell arrest at the G2/M stage. The preliminary results showed phosphorus(V) corrole complex is a good candidate for photodynamic therapy (PDT) of tumors. [ABSTRACT FROM AUTHOR]

Development of therapeutic systems to treat glioblastoma, the most common and aggressive brain tumor, belongs to priority tasks in cancer research. We have synthesized colloidally stable magnetic nanoparticles (Dh=336 nm) coated with doxorubicin (Dox) conjugated copolymers of N,N‐dimethylacrylamide and either N‐acryloylglycine methyl ester or N‐acryloylmethyl 6‐aminohexanoate. The terminal carboxyl groups of the copolymers were reacted with alendronate by carbodiimide formation. Methyl ester groups were then transferred to hydrazides for binding Dox by a hydrolytically labile hydrazone bond. The polymers were subsequently bound on the magnetic nanoparticles through bisphosphonate terminal groups. Finally, the anticancer effect of the Dox‐conjugated particles was investigated using the U‐87 glioblastoma cell line in terms of particle internalization and cell viability, which decreased to almost zero at a concentration of 100 μg of particles per ml. These results confirmed that poly(N,N‐dimethylacrylamide)‐coated magnetic nanoparticles can serve as a solid support for Dox delivery to glioblastoma cells. [ABSTRACT FROM AUTHOR]

Coordination of arenophilic Cp*Ru+ (Cp*=η5‐C5Me5) fragment to pendant aromatic ring(s) of either benzylferrocene (1) or dibenzylferrocene (2) gave air‐ and water‐stable dinuclear (4) or trinuclear (6) ferrocene‐ruthenium conjugates. The complexes were characterized by NMR, ESI‐MS, cyclic voltammetry (CV), elemental analysis, and the molecular structure of 4 was established by single crystal X‐ray diffraction. Contrary to the starting ferrocenes 1 and 2, conjugates 4 and 6 showed significant in vitro anticancer activity (up to IC50 0.6±0.2 μM) against various cancer cell lines (A2780, SK‐OV‐3, MDA‐MB‐231). Differential pulse voltammetry (DPV) showed that the intracellular accumulation of 4 was approximately twice that of 6 in all studied cell lines, which corresponds to a higher cytotoxicity of 4. [ABSTRACT FROM AUTHOR]

By virtue of an efficient rhodium(III)‐catalyzed redox‐neutral C−H activation/ring‐opening of a strained ring/[4+2] annulation cascade of N‐methoxybenzamides with propargyl cycloalkanols, diverse 3‐acyl isoquinolin‐1(2H)‐ones were directly obtained in good yields and with excellent functional group compatibility. Additionally, their antitumor activities against various human cancer cells including HepG2, A549, MCF‐7 and SH‐SY5Y were evaluated and the action mechanism of the selected compound was also investigated in vitro. The results revealed that these products possessed a potent efficacy, by inhibiting proliferation and inducing apoptosis in a time‐dependent and dose‐dependent manner, suggesting that such compounds can serve as promising candidates for anti lung cancer drug discovery. [ABSTRACT FROM AUTHOR]

This article, published in ChemPlusChem, discusses the synthesis, stability studies, and anticancer activity of 5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds. The article refers to these compounds as "Supergold," a gender-neutral warrior with superpowers that fights against cancer. The golden armor and sword of Supergold symbolize the pharmacological power of the gold atom, while the gold-thiosemicarbazones molecules engraved on the shield represent the warrior's coat of arms. Supergold selectively destroys different cancer cells. The article provides more information on this topic and is authored by Esteban Rodríguez‐Arce, María Contel, and their colleagues. [Extracted from the article]

A series of Pt(II) complexes trans‐[Pt(PPh2allyl)2(κ1‐S‐SR)2], 1, PPh2allyl=allyldiphenylphosphine, SR=pyridine‐2‐thiol (Spy, 1 a), 5‐(trifluoromethyl)‐pyridine‐2‐thiol (SpyCF3‐5, 1 b), pyrimidine‐2‐thiol (SpyN, 1 c), benzothiazole‐2‐thiol (Sbt, 1 d), benzimidazole‐2‐thiol (Sbi, 1 e), were synthesized. They were characterized by NMR, HR ESI‐MS, and X‐ray crystallography. Treatment of human cancer cell lines (A549, SKOV3, MCF‐7) with these complexes resulted in promising antitumor effects in comparison with cisplatin. These compounds showed suitable selectivity between tumorigenic and non‐tumorigenic (MCF‐10 A) cell lines. Analyses of cell cycle progression and apoptosis were conducted for 1 a, the most cytotoxic compound, to screen dose/time response and to study the antiproliferative mechanism. An electrophoresis mobility shift assay was performed to assess the direct interaction of 1 a with DNA and the strong genotoxic ability was indicated through the comet assay method. [ABSTRACT FROM AUTHOR]

Anticancer-active RuII-η6-p-cymene complexes of bioactive 2-pyridinecarbothioamide ligands have been shown to have high selectivity for plectin and can be administered orally. Reported herein is the functionalization of a 2-pyridinecarbothioamide with a sulfonamide group and its conversion into M-η6-p-cymene complexes (M = Ru, Os). The presence of a sulfonamide moiety in many organic drugs and metal complexes endows these agents with interesting biological properties and can transform the latter into multi-targeted agents. The compounds were characterized with standard methods and the in vitro anticancer activity data was compared with studies on the hydrolytic stability of the complexes and their reactivity to small biomolecules. A molecular modeling study revealed plausible modes of binding of the complexes in the catalytic pocket of carbonic anhydrase II. [ABSTRACT FROM AUTHOR]

A new 4-ethynylpyridine 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based ligand L, which was synthesized by means of the Sonogashira coupling method, was used to obtain two new [2+2] iridium-based metallarectangles, 3 and 4. Ligand L and metallarectangles 3 and 4 were fully characterized through various analytical techniques. The structure of rectangle 4 was further confirmed by single-crystal X-ray diffraction analysis, which showed the formation of an expected [2+2] supramolecule, in which the iridium metal centers were bridged with ligand L to form the desired metallarectangle 4. In the context of the growing biological interest in metallarectangles, rectangle 4 was found to be highly active against two types of cancer cells, with IC50 values almost threefold superior to those of cisplatin. Both 3 and 4 showed dose-dependent abilities to bind bovine serum albumin and salmon sperm DNA; this indicated their tendency to interact with such biomolecules as a potential mode of action. [ABSTRACT FROM AUTHOR]

Hydroxypyr(id)ones constitute an emerging platform for the design of drug molecules, owing to their favorable biocompatibility and toxicity profiles. Herein, [RuII(η6-p-cymene)] complexes with 3-hydroxy-2-pyridinone functionalized with morpholine and thiomorpholine, as a means often used in medicinal chemistry to alter the physicochemical properties of drug compounds, are reported. The compounds underwent hydrolysis of the Ru−Cl bond and the aqua species were stable for up to 48 h in aqueous solution, as observed by 1H NMR spectroscopy and ESI-MS. The compounds formed adducts with amino acids and proteins through cleavage of the pyridinone ligand. Binding experiments to the nucleosome core particle by means of X-ray crystallography revealed similar reactivity and exclusive binding to histidine moieties of the histone proteins. Preliminary cyclin-dependent kinase 2 (CDK2)/cyclin A kinase inhibitory studies revealed promising activity similar to that of structurally related organometallic compounds. [ABSTRACT FROM AUTHOR]

Four novel chelators ( L1- L4) and their 89zirconium complexes were prepared and compared with the 89zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The 89Zr- L4 complex showed similar stability to that of 89Zr-DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89Zr- L4 had similar pharmacokinetic behavior to that of 89Zr-DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 ( L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89Zr- L5-trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2±2.25) and a high tumor specificity that was comparable to the performance of 89Zr-DFO-trastuzumab. [ABSTRACT FROM AUTHOR]

In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2-heteroaryl-[1,2,4]triazolo[1,5- c]quinazoline-5(6 H)-thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2-(3-heteroaryl-[1,2,4]triazol-5-yl)phenyl]amines with carbon disulfide, potassium ethyl xanthogenate, or aryl isothiocyanates, and in situ reaction of 2-isothiocyanatobenzonitrile with hydrazides. A series of N- R-2-[(2-heteroaryl-[1,2,4]triazole-[1,5- c]quinazoline-5-yl)thio]acetamides were obtained by aminolysis of the corresponding acetic acids and alkylation of potassium thiolates with N- R-2-chloroacetamides. It was established that some potassium thiolates, 4 a- 4 d, 4 h, and 4 i, had high antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration of 12.5 μg mL−1 and minimum bactericidal concentration of 25 μg mL−1, which exceeded the values for trimethoprim. In addition, {2-[3-(1 H-indole-2-yl)-1 H-1,2,4-triazol-5-yl]phenyl}amine 2 i was investigated in the concentration range 100-0.01 μ M at 59 lines of nine cancer cell types, and showed a mean effective concentration at 3.12-7.03 μ M and cytotoxic effect at 15.56-67.38 μ M. The possible mechanisms of activity were predicted by molecular docking studies to S. aureus dihydrofolate reductase and epidermal growth factor receptor kinase. [ABSTRACT FROM AUTHOR]

Folic acid has emerged as an interesting cell-targeting moiety and a number of drugs have been conjugated to folate. In this context, new conjugates of β-cyclodextrins with folate have been synthesised as drug carriers to improve their selectivity for cells overexpressing the folic acid receptor. In particular, both 3- and 6-functionalised β-cyclodextrins, linked to the α- or γ-carboxylic group of folic acid, have been synthesised and fully characterised. As a proof of concept, the antitumour platinum(IV) complex cis- trans- cis-[PtCl2(CH3CO2)2(adamantylamine)(NH3)] (LA-12) has been used as a guest drug. The LA-12-cyclodextrin inclusion complexes have been tested on tumour cells. In the presence of cyclodextrin-folate conjugates, LA-12 exhibited IC50 values four times smaller than those of LA-12 alone in MDA-MB-231 cells, which overexpress folic acid receptors on their membrane. No improvement of LA-12 cytotoxicity was found in control tumour cells that do not overexpress the folate receptor. Thus, the non-covalent approach, based on inclusion complexes with functionalised cyclodextrins, looks very promising for drug targeting. [ABSTRACT FROM AUTHOR]

The properties of mesoporous silica nanoparticles (MSN) (biocompatibility, surface area, particle diameter, mesoporous structure, and ease of functionalization) are reviewed regarding their benefits for the construction of cancer-targeting drug delivery systems, with an overview of literature reports within this research area. Intrinsic properties characteristic of tumor tissues (enhanced permeability and retention effect, overexpressed receptors, and acidic extracellular pH) are further discussed which can be utilized for cancer targeting. Recent literature reports are also accounted concerning MSN-based cancer targeting that takes advantage of characteristics of the tumor environment and also nanotherapeutics capable of stimulus (acidification, exposure to light irradiation, magnetic field) responsive drug delivery. Finally, gene therapy approaches for cancer treatment and MSN-based gene delivery vectors are reviewed. The research on mesoporous silicates possesses great potential for the development of complex multipurpose nanotherapeutics for simultaneous application in effective targeted treatment and imaging of cancer tissues. [ABSTRACT FROM AUTHOR]

Two hexacationic pentamethylcyclopentadienyl rhodium(III) and iridium(III) metalla-prisms, [(η5-C5Me5)6M6(μ3-tpt-κ N)2(μ4-C6HRO4-κ O)3]6+ (tpt=2,4,6-tri-(pyridin-4-yl)-1,3,5-triazine; R=(CH2)10CH3; M=Rh, [ 3]6+; M=Ir, [ 4]6+) isolated as their triflate salts, have been synthesised from the dinuclear complexes (η5-C5Me5)2M2(μ4-C6HRO4-κ O)Cl2 (M=Rh, 1; M=Ir, 2) and AgCF3SO3. The antiproliferative activity of the neutral and cationic complexes has been evaluated in vitro in human cancer cell lines. The positively charged metalla-prisms appear to target mitochondria, which ultimately induce apoptosis in cancer cells. All biological studies suggest that the rhodium derivative [ 3][CF3SO3]6 possesses excellent activities, not only in vitro but also in vivo in tumour-induced C57L6/J mice. [ABSTRACT FROM AUTHOR]

The elaboration, characterisation and efficiency of potential two-photon-excited photodynamic therapy (PDT) treatment of new poly(d,l-lactide-co-glycolide) nanoparticles loaded with ruthenium(II) complexs are presented. The materials are based on the encapsulation of RuII complexes through an all-biocompatible process. The size of the nanoparticles is around 100 nm. The internal concentration is several orders of magnitude higher than the overall concentration, which leads to a more efficient and targeted effect. The therapeutic potential for PDT of these nanoparticles has been studied in vitro on C6 glioma cells. [ABSTRACT FROM AUTHOR]

The introduction of a hydrophobic group at position 7 of 9-fluorenone-2-carboxylic acid generates new tubulin binders, the design of which is suggested by modeling studies. The synthesis is based on the use of 2,7-dibromo-fluorenone as starting material. The antiproliferative activity on two different cell lines, fluorescent microscopy, flow cytometry, and sedimentation assay tests confirmed the supposed mechanism. [ABSTRACT FROM AUTHOR]

Stimuli-responsive micellar nanoparticles are gaining considerable attention in the field of drug delivery because of their great advantages of high efficiency in tumor accumulation through the enhanced permeability and retention effect and rapid drug release. In this study, a novel catechol moiety-containing amphiphilic, biodegradable polymeric carrier, monomethoxy poly(ethylene glycol)- block-poly(ε-caprolactone)- block-poly( L-lysine)- graft-[3-(3,4-dihydroxyphenyl)propionic acid], was employed for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. The strategy is based on the facile conjugation of BTZ to catechol-containing polymeric carriers through boronate formation, which could dissociate in acidic environments to liberate its payload BTZ to inhibit proteasome function. This reducing BTZ-catechol interaction with decreasing pH value was demonstrated by microcalorimetry analysis using isothermal titration calorimetry. Notably, the obtained micellar BTZ complex that self-assembled from drug-loaded amphiphilic polymer was internalized effectively by MCF-7 breast cancer cells and resulted in significant 26S proteasome inhibition. Furthermore, the micellar BTZ complex induced remarkable apoptosis on MCF-7 and HeLa cancer cells and exhibited little toxicity on HEK293 normal cells. More importantly, systemic delivery of micellar BTZ complex prolonged its blood circulation and resulted in significant accumulation in the tumor site relative to free drug, thus suggesting therapeutic promise for micellar BTZ delivery in cancer therapy. [ABSTRACT FROM AUTHOR]

In the search for novel metal-based pharmaceuticals, ruthenium-catalysed 1,3-dipolar cycloaddition is used to functionalise a series of palladium and platinum N-heterocyclic carbene complexes. This strategy was applied to the conjugation of amino acid, polyethylene glycol and oestradiol derivatives with the aim of enhancing chemical diversity and introducing specific features (e.g., water solubility, cell targeting). Antiproliferative activities of the different complexes were assayed against several cancer cell lines (KB, MCF7, HCT116, PC3, SKOV3, OVCAR8, HL60) and healthy cell lines (MRC5, VERO, EPC), which established their efficiency. The ease of the structural derivatisation thus renders these complexes attractive metal-based systems for the development of selective targeted metal-hybrid anticancer drugs. [ABSTRACT FROM AUTHOR]

Two ruthenium(II) complexes [Ru(phen)2(tip)](ClO4)2 ( 1) and [Ru(bpy)2(tip)](ClO4)2 ( 2; phen=1,10-phenanthroline, bpy=2,2'-bipyridine, tip=2-thiophenimidazo[4,5- f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, 1H NMR spectroscopy, and electrospray ionization-mass spectrometry to explore the role of metal complexes as novel telomeric quadruplex stabilizers. The different quadruplex binding properties of these compounds were evaluated by absorption and emission analyses, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, NMR spectroscopy, and molecular modeling. The results show that both complexes can well induce and stabilize different G-quadruplex structures using a 1:1 [quadruplex]/[complex] binding mode ratio. Complex 1 exhibits higher interaction ability at 1.43×106 M−1 binding affinity and superior G-quadruplex selectivity over duplex DNA through multiple interaction (mainly intercalating) with the G-quadruplex at the 3'-terminal face. Furthermore, polymerase chain reaction (PCR)-stop assay, electrophoretic mobility shift assay, telomerase repeat amplification protocol, and MTT assay demonstrate that complex 1 not only can stabilize dimer forms of the G-quadruplex at low concentrations but also exhibit better inhibitory activity for telomerase and cancer cells. The results suggest that complex 1 may be a potential telomerase inhibitor for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Cover Feature: Rh(III)-Catalyzed Redox-Neutral [4+2] Annulation for Direct Assembly of 3-Acyl Isoquinolin-1(2H)-ones as Potent Antitumor Agents (ChemPlusChem 3/2020) Keywords: antitumor agents; cell apoptosis; C-H functionalization; isoquinolin-1(2H)-one; rhodium(III) catalysis EN antitumor agents cell apoptosis C-H functionalization isoquinolin-1(2H)-one rhodium(III) catalysis 388 388 1 04/02/20 20200301 NES 200301 B The cover feature shows b a new and efficient rhodium(III)-catalyzed redox-neutral C-H activation/ring-opening of strained ring/[4+2] annulation cascade of I N i -methoxybenzamides with propargyl cycloalkanols, providing a direct access to diverse 3-acyl isoquinolin-1(2 I H i )-ones as potential anti-lung-cancer drugs. Antitumor agents, cell apoptosis, C-H functionalization, isoquinolin-1(2H)-one, rhodium(III) catalysis. [Extracted from the article]

A picture of Ru polypyridyl complex with 1,10-phenanthroline as anancillary ligand is presented.

Hydroxypyr(id)ones constitute an emerging platform for the design of drug molecules, owing to their favorable biocompatibility and toxicity profiles. Herein, [Ru II (η 6 -p-cymene)] complexes with 3-hydroxy-2-pyridinone functionalized with morpholine and thiomorpholine, as a means often used in medicinal chemistry to alter the physicochemical properties of drug compounds, are reported. The compounds underwent hydrolysis of the Ru-Cl bond and the aqua species were stable for up to 48 h in aqueous solution, as observed by 1 H NMR spectroscopy and ESI-MS. The compounds formed adducts with amino acids and proteins through cleavage of the pyridinone ligand. Binding experiments to the nucleosome core particle by means of X-ray crystallography revealed similar reactivity and exclusive binding to histidine moieties of the histone proteins. Preliminary cyclin-dependent kinase 2 (CDK2)/cyclin A kinase inhibitory studies revealed promising activity similar to that of structurally related organometallic compounds., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The frontispiece shows a TEM image of a mesoporous silica nanoparticle (MSN) and a graphical representation of MSN‐based nanoconstructs for stimuli‐responsive delivery of mesopore‐loaded therapeutic molecules and targeted delivery of drugs and therapeutic genes to cancer cells through specific recognition of cancer‐overexpressed receptors. The Minireview by Nikola Ž. Knežević and Jean‐Olivier Durand on page 26 discusses modalities for targeted treatment of cancer with an overview of recent MSN‐based effective designs for therapeutic and diagnostic anticancer applications. [ABSTRACT FROM AUTHOR]

Four novel chelators ( L1 - L4 ) and their 89 zirconium complexes were prepared and compared with the 89 zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr 4+ ions with coordination numbers between six and eight. The 89Zr- L4 complex showed similar stability to that of 89 Zr-DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89 Zr- L4 had similar pharmacokinetic behavior to that of 89 Zr-DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 ( L5 ) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89 Zr- L5 -trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2 ± 2.25) and a high tumor specificity that was comparable to the performance of 89 Zr-DFO-trastuzumab.

Two hexacationic pentamethylcyclopentadienyl rhodium(III) and iridium(III) metalla-prisms, [(η 5 -C 5 Me 5 ) 6 M 6 (μ 3 -tpt-κN) 2 (μ 4 -C 6 HRO 4 -κO) 3 ] 6+ (tpt=2,4,6-tri-(pyridin-4-yl)-1,3,5-triazine; R=(CH 2 ) 10 CH 3 ; M=Rh, [3] 6+ ; M=Ir, [4] 6+ ) isolated as their triflate salts, have been synthesised from the dinuclear complexes (η 5 -C 5 Me 5 ) 2 M 2 (μ 4 -C 6 HRO 4 -κO)Cl 2 (M=Rh, 1; M=Ir, 2) and AgCF 3 SO 3 . The antiproliferative activity of the neutral and cationic complexes has been evaluated in vitro in human cancer cell lines. The positively charged metalla-prisms appear to target mitochondria, which ultimately induce apoptosis in cancer cells. All biological studies suggest that the rhodium derivative [3][CF 3 SO 3 ] 6 possesses excellent activities, not only in vitro but also in vivo in tumour-induced C57L6/J mice., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)