NDLI: Novel metal(ii) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

Please wait, while we are loading the content...

Evidence for a preferential intramolecular oxidative addition in Ni-catalyzed cross-coupling reactions and their impact on chain-growth polymerizations

Denaturation of dsDNA immobilised at a negatively charged gold electrode is not caused by electrostatic repulsion

Photoelectron spectroscopy of solvated electrons in alcohol and acetonitrile microjets

Lewis-base silane activation: from reductive cleavage of aryl ethers to selective ortho-silylation

Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

Clathrochelate-based bipyridyl ligands of nanoscale dimensions: easy-to-access building blocks for supramolecular chemistry

Transparent and ultra-bendable all-solid-state supercapacitors without percolation problems

A photoisomerization-coupled asymmetric Stetter reaction: application to the total synthesis of three diastereomers of (−)-cephalimysin A

Asymmetric NHC-catalyzed synthesis of α-fluoroamides from readily accessible α-fluoroenals

Tuning colourimetric indicator displacement assays for naked-eye sensing of pyrophosphate in aqueous media

A surface site interaction model for the properties of liquids at equilibrium

Phosphine oxide functional group based three-station molecular shuttle

Kinetics and mechanisms of oxidative cleavage of HIV RRE RNA by Rev-coupled transition metal–chelates

Single molecule magnetism in a family of mononuclear β-diketonate lanthanide(iii) complexes: rationalization of magnetic anisotropy in complexes of low symmetry

Modulating the packing of [Cu₂₄(isophthalate)₂₄] cuboctahedra in a triazole-containing metal–organic polyhedral framework

Long lived charge separation in iridium(iii)-photosensitized polyoxometalates: synthesis, photophysical and computational studies of organometallic–redox tunable oxide assemblies

Systematic modulation and enhancement of CO₂ : N₂ selectivity and water stability in an isoreticular series of bio-MOF-11 analogues

Homoconjugation in diporphyrins: excitonic behaviors in singly and doubly linked Zn(ii)porphyrin dimers

Cyclic benzobisimidazolium derivative for the selective fluorescent recognition of HSO₄⁻via a combination of C–H hydrogen bonds and charge interactions

Aromatic reactivity revealed: beyond resonance theory and frontier orbitals

Exploring frontiers of high surface area metal–organic frameworks

Three coordinate models for the binuclear Cu_A electron-transfer site

A dynamic, luminescent and entangled MOF as a qualitative sensor for volatile organic solvents and a quantitative monitor for acetonitrile vapour

Zero-field slow magnetic relaxation from single Co(ii) ion: a transition metal single-molecule magnet with high anisotropy barrier

Structural dependence of the optical properties of narrow bandgap semiconductors with orthogonal donor–acceptor geometries

Identification of Bi₂WO₆ as a highly selective visible-light photocatalyst toward oxidation of glycerol to dihydroxyacetone in water

Sequential and phototriggered supramolecular self-sorting cascades using hydrogen-bonded motifs

Binding energies of micro-hydrated carbohydrates: measurements and interpretation

Novel metal(ii) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

Double-channel photosystems with antiparallel redox gradients: templated stack exchange with porphyrins and phthalocyanines

Time-resolved monitoring of dynamic self-assembly of Au(i)-thiolate coordination polymers

Metal ions triggered ligase activity for rolling circle amplification and its application in molecular logic gate operations

Cooperativity between steric repulsion and crossed diene coordination governs the enantioselectivity in rhodium(i)/chiral, 1,4- and 1,5-diene-catalysed 1,4-addition reaction: a DFT study

Regiodivergent reductive coupling of 2-substituted dienes to formaldehyde employing ruthenium or nickel catalyst: hydrohydroxymethylation via transfer hydrogenation

Revealing the P–B coupling event in the rhodium catalysed dehydrocoupling of phosphine–boranes H₃B·PR₂H (R = ^tBu, Ph)

Cross-conjugation of DNA, proteins and peptides via a pH switch

Isomeric and chemical consequences of the direct magnesiation of 1,3-benzoazoles using β-diketiminate-stabilized magnesium bases

Disulfide reductive elimination from an iron(iii) complex

Back cover

Chemical Science Vol - 4 Issue - 3

Chemical Science Vol - 4 Issue - 2

Chemical Science Vol -3

Chemical Science Vol -2

Chemical Science Vol -1

Novel metal(ii) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

Content Provider	Royal Society of Chemistry (RSC)
Author	Meier, Samuel M. Hanif, Muhammad Jakupec, Michael A. Arion, Vladimir B. Novak, Maria Adhireksan, Zenita Davey, Curt A. Pichler, Verena Jirkovsky, Elisabeth Keppler, Bernhard K. Hartinger, Christian G.
Copyright Year	2013
Abstract	A novel series of organometallic antitumour agents based on RuII and OsII complexes containing N-substituted 2-pyridinecarbothioamides (PCAs) has been synthesized and characterized. To the best of our knowledge, this is the first report of organometallic anticancer compounds with an S,N-bidentate ligand system. While the ligands showed activity as gastric mucosal protectants and low acute toxicity in vivo (J. Med. Chem., 1990, 33, 327–336), coordination leads to highly antiproliferative metallodrugs, depending on lipophilicity and steric demand, in colon carcinoma and non-small lung cancer cell lines with intrinsic chemoresistances. The most lipophilic and smallest congeners are the most effective with IC50 values in the low micromolar range. This new family of potential metallodrugs features exceptional stability in hydrochloric acid (60 mM), characterized by complete suppression of hydrolysis and low reactivity towards biological nucleophiles. Therefore, their unexpected aqueous chemistry renders this family of antiproliferative agents suitable for oral administration. An unprecedented feature is their ability to form transient thioketone-bridged dimers in aqueous solution upon hydrolysis, which is believed to minimize deactivation by biological nucleophiles. However, the biological effect seems to be caused by the monomer as observed with crystallographic studies of the nucleosome core particle (NCP), which revealed that [chlorido(η6-p-cymene)(N-phenyl-2-pyridinecarbothioamide)osmium(II)] chloride and [chlorido(η6-p-cymene)(N-fluorophenyl-2-pyridinecarbothioamide)osmium(II)] chloride react at two types of binding sites on the histone proteins. The adducts form at histidine side chains located on the nucleosome surface and the inner cleft of the nucleosome in the midst of an extensive histone–histone interface, suggesting interference with chromatin activity as a possible mode of action of these compounds. Additionally, ligand-based S → O exchange allows for a potential dual-mode of action by targeting DNA (J. Med. Chem., 2009, 52, 7753–7764). The quantitative estimates of drug-likeness (QED) for this family of compounds revealed a similar drug-likeness compared to erlotinib, tamoxifen, imatinib and sorafenib.
Starting Page	1837
Ending Page	1846
Page Count	10
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	4
Issue Number	4
Journal	Chemical Science
DOI	10.1039/c3sc22294b
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Acid Chromatin Imatinib Carcinoma Ligand P-Cymene Nucleosome Colorectal cancer Tamoxifen Osmium Hydrolysis Organic chemistry Chloride Histidine Erlotinib Organometallic chemistry DNA Quantum electrodynamics Sorafenib IC50 Monomer Histone Lipophilicity Non-small-cell lung carcinoma
Content Type	Text
Resource Type	Article
Subject	Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Novel metal(II) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

Structure-activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity.

Synthesis, physicochemical and biological evaluation studies of ruthenium(II) and osmium(II) anticancer organometallic complexes

Potent organometallic osmium compounds induce mitochondria-mediated apoptosis and S-phase cell cycle arrest in A549 non-small cell lung cancer cells

In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η⁶-p-cymene)Cl₂(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

Structure–activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity

Sweetening ruthenium and osmium: organometallic arene complexes containing aspartame

Design of osmium arene anticancer complexes

Novel metal(ii) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

Similar Documents

Novel metal(II) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

Structure-activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity.

Synthesis, physicochemical and biological evaluation studies of ruthenium(II) and osmium(II) anticancer organometallic complexes

Potent organometallic osmium compounds induce mitochondria-mediated apoptosis and S-phase cell cycle arrest in A549 non-small cell lung cancer cells

In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

Structure–activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity

Sweetening ruthenium and osmium: organometallic arene complexes containing aspartame

Design of osmium arene anticancer complexes

Novel metal(ii) arene 2-pyridinecarbothioamides: a rationale to orally active organometallic anticancer agents

In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η⁶-p-cymene)Cl₂(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas