Abstract The breast cancer stem cell (CSC) and bulk potency of a series metallopeptides containing dichloro(1,10‐phenanthroline)copper(II) various organelle‐targeting peptide sequences is reported. mitochondria‐targeting metallopeptide 1 exploits the higher mitochondrial load in CSCs over corresponding non‐CSCs vulnerability to damage potently selectively kill CSCs. Strikingly, reduces formation size mammospheres greater extent than salinomycin, an established CSC‐potent agent. Mechanistic...

Abstract The preparation of multinuclear metal complexes offers a route to novel anticancer agents and delivery systems. potency triangular complex containing three platinum atoms, Pt‐3 , towards breast cancer stem cells (CSCs) is reported. trinuclear platinum(II) complex, exhibits selective toxicity CSCs over bulk non‐tumorigenic cells. Remarkably, inhibits the formation, size, viability mammospheres better extent than salinomycin, an established CSC‐potent agent, cisplatin carboplatin,...

Here we report the breast cancer stem cell (CSC) potency of a reactive oxygen species (ROS)-generating manganese(<sc>ii</sc>)-phenanthroline complex bearing diclofenac, nonsteriodial anti-inflammatory drug.

Abstract Four copper(II) complexes, 1 – 4 containing regioisomeric vanillin Schiff base derivatives and the nonsteroidal anti‐inflammatory drug (NSAID), naproxen, were synthesised characterised. All complexes effectively cleave DNA in cell‐free systems, with displaying highest nuclease activity. binding studies suggest that binds to via grooves prior inducing oxidative cleavage. Three of ( , 3 ) indiscriminately kill cancer stem cell (CSC)‐enriched cells (HMLER‐shEcad) bulk (HMLER) at...

Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties, 1-4, are shown to kill bulk cancer cells stem (CSCs) with low micromolar potency. The most effective complex, 1, elicits its cytotoxic effect by elevating the intracellular reactive oxygen species (ROS) levels inhibiting cyclooxygenase-2 (COX-2) expression.

The cytotoxic properties of a series nickel(II)-dithiocarbamate phenanthroline complexes is reported. 1-6 kill bulk cancer cells and stem (CSCs) with micromolar potency. Two the complexes, 2 6, twice as many breast cell (CSC)-enriched HMLER-shEcad compared to CSC-depleted HMLER cells. Complex inhibits mammosphere formation similar extent salinomycin (a CSC-specific toxin). Detailed mechanistic studies suggest that induces CSC death by necroptosis, programmed form necrosis. Specifically,...

We report the cancer stem cell (CSC) potency of a novel series copper(ii)-phenanthroline complexes bearing nonsteriodial anti-inflammatory drugs: naproxen, tolfenamic acid, and indomethacin (2a-3c). Two complexes, 2a 3c, kill breast CSC-enriched HMLER-shEcad cells (grown in both monolayer three-dimensional cultures) to significantly better extent than salinomycin, well-established CSC toxin. The most potent complex series, 3c induces its cytotoxic effect by generating intracellular reactive...

Abstract We report the potency against cancer stem cells (CSCs) of a new cobalt(III)‐cyclam complex ( 1 ) that bears nonsteroidal anti‐inflammatory drug, naproxen. The displays selective for breast CSC‐enriched HMLER‐shEcad over CSC‐depleted HMLER cells. Additionally, it inhibited formation three‐dimensional tumour‐like mammospheres, and reduced their viability to greater extent than clinically used drugs (vinorelbine, cisplatin paclitaxel). anti‐mammosphere was enhanced under...

Abstract Membrane‐lytic peptides offer broad synthetic flexibilities and design potential to the arsenal of anticancer therapeutics, which can be limited by cytotoxicity noncancerous cells induction drug resistance via stress‐induced mutagenesis. Despite continued research efforts on membrane‐perforating for antimicrobial applications, success in peptide therapeutics remains elusive given muted distinction between cancerous normal cell membranes challenge degradation neutralization upon...

Abstract The cancer stem cell (CSC) toxicity and mechanism of action a series iridium(III) complexes bearing polypridyl charged 1‐methyl‐2‐(2‐pyridyl)pyridinium ligands, 1 – 4 is reported. most effective complex (containing 1,10‐phenanthroline), 3 , kills CSCs bulk cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations single dose. Encouragingly, also inhibits mammopshere formation to similar extent as salinomycin,...

Copper(ii) coordination complexes, 1 and 2, containing nonsteroidal anti-inflammatory drugs (NSAIDs) potently kill breast cancer stem cells (CSCs) bulk cells. Although detailed biological studies have been conducted to shed light on their mechanism of cytotoxicity, little is known about molecular level action. This biophysical study, aided by the preparation a fluorophore-containing analogue, 3, reveals that complexes operate undergoing reduction copper(i) form releasing associated NSAIDs.

We report a novel series of cobalt(<sc>iii</sc>)-polypridyl complexes that can selectively release diflunisal, nonsteroidal anti-inflammatory drug, under reducing conditions.

Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs a subtype of with the ability differentiate, self-renew, and form secondary or tertiary tumors. Current treatments—including chemotherapy, radiation, surgery—effectively remove bulk but unable eliminate CSCs. Here, we present synthesis, characterization, anti-CSC properties cobalt(III)–cyclam complex bearing two tolfenamic acid moieties, 3. Notably, 3 displays sub-micromolar potency towards breast cells. Detailed...

We report the synthesis and characterisation of mono- di-nuclear cobalt(<sc>ii</sc>) complexes (<bold>1–3</bold>) containing <bold>L1</bold>, a polypyridyl ligand with pyrazole moieties.

Cancer stem cells (CSCs) are thought of as a clinically pertinent subpopulation tumors, partly responsible for cancer relapse and metastasis. Research programs aimed at discovering anti-CSC agents have largely focused on biologics purely organic molecules. Recently, we showed that family redox-active copper(II) complexes with phenanthroline-based ligands nonsteroidal anti-inflammatory drugs (NSAIDs) such indomethacin, capable potently selectively killing breast CSCs. Herein present analogous...

We report the anti-osteosarcoma and stem cell (OSC) properties of a nickel(II) complex, 1. Complex 1 displays similar potency towards bulk osteosarcoma cells OSCs, in micromolar range. Notably, or better OSC than clinically approved platinum(II) anticancer drugs cisplatin carboplatin two- three-dimensional cultures. Mechanistic studies revealed that induces death by necroptosis, an ordered form necrosis. The triggers necrosome-dependent mitrochondrial membrane depolarisation propidium iodide...

Abstract The preparation of multinuclear metal complexes offers a route to novel anticancer agents and delivery systems. potency triangular complex containing three platinum atoms, Pt‐3 , towards breast cancer stem cells (CSCs) is reported. trinuclear platinum(II) complex, exhibits selective toxicity CSCs over bulk non‐tumorigenic cells. Remarkably, inhibits the formation, size, viability mammospheres better extent than salinomycin, an established CSC‐potent agent, cisplatin carboplatin,...

Abstract The breast cancer stem cell (CSC) and bulk potency of a series metallopeptides containing dichloro(1,10‐phenanthroline)copper(II) various organelle‐targeting peptide sequences is reported. mitochondria‐targeting metallopeptide 1 exploits the higher mitochondrial load in CSCs over corresponding non‐CSCs vulnerability to damage potently selectively kill CSCs. Strikingly, reduces formation size mammospheres greater extent than salinomycin, an established CSC‐potent agent. Mechanistic...

Copper(II) complexes bearing nonsteroidal anti-inflammatory drugs (NSAIDs) are known to potently kill cancer stem cells (CSCs), a subpopulation of tumour with high metastatic and relapse fidelity. One the major disadvantages associated these copper(II) is their instability in presence strong cellular reductants (such as ascorbic acid). Here we present biologically stable copper(II)-NSAID complex containing bathocuproinedisulfonic acid disodium ligand two indomethacin moieties,...

A multi-nuclear, triangular-shaped palladium(<sc>ii</sc>) complex is shown to equipotently kill bulk cancer cells and stem (CSCs) in the micromolar range.

Metal-organic frameworks (MOFs) have been recently proposed as a new nanoscale drug delivery vector posing significant surface area and tunable chemo physical properties. The main procedure of encapsulation anticancer drugs into the MOFs are post synthetic methods (PSM), however that is time/energy consuming often not be reproducible in large scale. Further, PSM method would applicable without coating due to burst release. Herein, we report strategy incorporating hydrophobic natural...