Search

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29). The tests showed that diclofenac and the carborane-substituted oxindoles exhibited no cytotoxicity, the dichlorophenyl-substituted oxindole had moderate anti-cancer activity, while with the amidine this effect was strongly potentiated with activity mapping within low micromolar range. Compound 3 abolished the viability of selected colon cancer cell line MC38 preferentially through strong inhibition of cell division and moderate apoptosis accompanied by ROS/RNS depletion. Our findings suggest that carborane-based prodrugs could be a promising direction for new anti-cancer therapies. Inhibition assays for COX-1 and COX-2 revealed that while diclofenac had strong COX inhibition, the re-engineered carborane compounds demonstrated a varied range of anti-cancer effects, probably owing to both, COX inhibition and COX-independent pathways. [ABSTRACT FROM AUTHOR]

Phosphino hydrazones represent a versatile class of nitrogen‐containing phosphine ligands. Herein, we report a modular synthesis of phosphino hydrazone ligands by hydrazone condensation reaction of three different aryl hydrazines with 3‐(diphenylphosphino)propanal (PCHO). Complexation reactions of these phosphino hydrazone ligands with palladium(II) and platinum(II) were investigated and the catalytic activity of the palladium(II) complexes was explored in a Cu‐free Sonogashira cross‐coupling reaction achieving yields up to 96 %. Additionally it was shown that the catalytically active species is homogeneous. [ABSTRACT FROM AUTHOR]

The syntheses of the first B9‐connected carboranylphosphines (B9‐Phos) featuring two carboranyl moieties as well as access to B9‐Phos ligands with bulky electron‐donating substituents, previously deemed unattainable, is reported. The electrochemical properties of the B9‐Phos ligands were investigated, revealing the ability of the mesityl derivatives to form stabilized phosphoniumyl radical cations. The B9‐Phos ligands display an extremely electron‐releasing character surpassing that of alkyl phosphines and commonly used N‐heterocyclic carbenes. This is demonstrated by their very small Tolman electronic parameters (TEPs) as well as extremely low P−Se coupling constants. Cone angles and buried volumes attest to the high steric demand exerted by the (di)carboranyl phosphines. The dicarboranyl phosphine AuI complexes show superior catalytic performance in the hydroamination of alkynes compared to the monocarboranyl phosphine analogs. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities. [ABSTRACT FROM AUTHOR]

Invited for this month's cover is the group of Evamarie Hey‐Hawkins at Leipzig University. The cover picture shows the three different bonding modes (mono‐, bi‐ and tridentate) of the modular ligand towards palladium(II) or platinum(II), illustrated with Winston who kindly served as the model. The cat has three binding sites (mouth, front paws and hind paws = P, N and pyridine) to bind the metal dichloride fragment. When all three are used in a tridentate bonding mode, one chlorido ligand is cleaved off. Cover design by Dr. Christoph Selg. More information can be found in the Research Article by Evamarie Hey‐Hawkins and co‐workers. [ABSTRACT FROM AUTHOR]

Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. In the original publication [[1]], there was an error in Scheme 1 as published. References 1 Kazimir A., Schwarze B., Lönnecke P., Jelaca S., Mijatovi'c S., Maksimovi'c-Ivani'c D., Hey-Hawkins E. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. [Extracted from the article]

N, P Ligands, palladium, phosphino hydrazone, platinum, Sonogashira cross-coupling Keywords: N, P Ligands; palladium; phosphino hydrazone; platinum; Sonogashira cross-coupling EN N, P Ligands palladium phosphino hydrazone platinum Sonogashira cross-coupling 1 1 1 10/30/23 20231001 NES 231001 B The cover picture shows b the three different bonding modes (mono-, bi- and tridentate) of the modular ligand towards palladium(II) or platinum(II), illustrated with Winston who kindly served as model. Front Cover: Modular Synthesis of Phosphino Hydrazones and Their Use as Ligands in a Palladium-Catalysed Cu-Free Sonogashira Cross-Coupling Reaction (ChemPlusChem 10/2023). [Extracted from the article]

Keywords: Carboranes; Homogeneous Catalysis; Ligand Design; Phosphines; Strong Donors; Transition Metal Complexes EN Carboranes Homogeneous Catalysis Ligand Design Phosphines Strong Donors Transition Metal Complexes 1 1 1 03/23/23 20230327 NES 230327 B Carboranes b . Frontispiece: On the Edge of the Known: Extremely Electron-Rich (Di)Carboranyl Phosphines Carboranes, Homogeneous Catalysis, Ligand Design, Phosphines, Strong Donors, Transition Metal Complexes. [Extracted from the article]

B9-functionalized carboranylphosphines with bulky electron-donating substituents display an extremely electron-releasing character, as reported by Evamarie Hey-Hawkins et al. in their Research Article (e202218648). The compounds exert a high steric demand, which allows the mesityl derivatives to form stabilized phosphoniumyl radical cations. Keywords: Carborane; Homogene Katalyse; Ligandendesign; Phosphane; Übergangsmetallkomplexe DE Carborane Homogene Katalyse Ligandendesign Phosphane Übergangsmetallkomplexe 1 1 1 03/23/23 20230327 NES 230327 B Carboranes b . [Extracted from the article]