Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues.

Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.

LED-induced Ru-photoredox Pd-catalyzed C-H arylation of (6-phenylpyridin-2-yl)pyrimidines and heteroaryl counterparts.

N-heterocycles are essential building blocks and scaffolds in medicinal chemistry. A Pd-catalyzed, Ru-photoredox-mediated C-H arylation is applied herein, for converting a series of functionality-inclusive (6-phenylpyridin-2-yl)pyrimidines to single arylated derivatives, using phenyldiazonium tetrafluoroborate as aryl source. This green chemistry-compliant transformation is induced by LED light.

Catalysis of a Diels-Alder Reaction between Azachalcones and Cyclopentadiene by a Recyclable Copper(II)-PEIP Metal-Organic Framework.

Metal-organic frameworks (MOFs) have attracted considerable interest as emerging heterogeneous catalysts for organic transformations of synthetic utility. Herein, a Lewis-acidic MOF, {[Cu(PEIP)(5-NH-BDC)(DMF)]·7DMF}∞, denoted as Cu(ΙΙ)-PEIP, has been synthesized via a one-pot process and deployed as an efficient heterogeneous catalyst for a Diels-Alder cycloaddition. Specifically, the [4 + 2] cycloaddition of 13 substituted azachalcone dienophiles with cyclopentadiene has been investigated.

Gaining Insights on the Interactions of a Class of Decorated (2-([2,2'-Bipyridin]-6-yl)phenyl)platinum Compounds with c-Myc Oncogene Promoter G-Quadruplex and Other DNA Structures.

Organometallic molecules offer some of the most promising scaffolds for interaction with G-quadruplex nucleic acids. We report the efficient synthesis of a family of organoplatinum(II) complexes, featuring a 2-([2,2'-bipyridin]-6-yl)phenyl tridentate (N N C) ligand, that incorporates peripheral side-chains aiming at enhancing and diversifying its interaction capabilities. These include a di-isopropyl carbamoyl amide, a morpholine ethylenamide, two enantiomeric proline imides and an oxazole.

Recent Developments in Small-Molecule Ligands of Medicinal Relevance for Harnessing the Anticancer Potential of G-Quadruplexes.

G-quadruplexes, a family of tetraplex helical nucleic acid topologies, have emerged in recent years as novel targets, with untapped potential for anticancer research. Their potential stems from the fact that G-quadruplexes occur in functionally-important regions of the human genome, such as the telomere tandem sequences, several proto-oncogene promoters, other regulatory regions and sequences of DNA (e.g.

A Novel Conjugate of Bis[((4-bromophenyl)amino)quinazoline], a EGFR-TK Ligand, with a Fluorescent Ru(II)-Bipyridine Complex Exhibits Specific Subcellular Localization in Mitochondria.

The epidermal growth factor receptor (EGFR) is a key target in anticancer research, whose aberrant function in malignancies has been linked to severe irregularities in critical cellular processes, including cell cycle progression, proliferation, differentiation, and survival. EGFR mutant variants, either transmembrane or translocated to the mitochondria and/or the nucleus, often exhibit resistance to EGFR inhibitors. The ability to noninvasively image and quantify EGFR provides novel approaches in the detection, monitoring, and treatment of EGFR-related malignancies.

Investigation of 'Head-to-Tail'-Connected Oligoaryl N,O-Ligands as Recognition Motifs for Cancer-Relevant G-Quadruplexes.

Oligomeric compounds, constituted of consecutive ,-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C-H activation of the formed oxazoles and their subsequent C-C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, 'head-to-tail'-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes.

Inhibition of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 2 (Cdk2) by platinum(II) phenanthroline complexes.

Unlabelled: Inhibition of protein kinases in the fight against disease remains a constant challenge for medicinal chemists, who have screened multitudes of predominantly planar organic scaffolds, natural and synthetic, to identify potent-albeit not always selective-kinase inhibitors. Herein, in an effort to investigate the potential biological utility of metal-based compounds as inhibitors against the cancer-relevant targets mitogen-activated protein kinase and cyclin-dependent kinase 2, we explore various parameters in planar platinum(II) complexes with substituted phenanthroline ligands and aliphatic diamine chelate co-ligands, to identify combinations that yield promising inhibitory activity. The individual ligands' steric requirements as well as their pattern of hydrogen bond donors/acceptors appear to alter inhibitory potency when modulated.

Identification of a potent activator of Akt phosphorylation from a novel series of phenolic, picolinic, pyridino, and hydroxamic zinc(II) complexes.

The discovery of small-molecule modulators of signaling pathways is currently a particularly active area of research. We aimed at developing unprecedented metal-based activators of Akt signaling which can potentially find applications as tools for regulating glucose metabolism downstream of Akt or serve as lead structures for developing antidiabetic drugs. In this context, a highly diverse library of 11 new zinc(II) complexes with phenolic, picolinic, pyridino, and hydroxamic ligands, all containing features beneficial for medicinal purposes, was prepared and screened in an assay that detected levels of phospho-Akt in lysates from NIH3T3 cells after treatment with the compounds.

Interaction of metal complexes with G-quadruplex DNA.

Guanine-rich sequences of DNA can assemble into tetrastranded structures known as G-quadruplexes. It has been suggested that these secondary DNA structures could be involved in the regulation of several key biological processes. In the human genome, guanine-rich sequences with the potential to form G-quadruplexes exist in the telomere as well as in promoter regions of certain oncogenes.

FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases.

Aging is a risk factor for the development of adult-onset neurodegenerative diseases. Although some of the molecular pathways regulating longevity and stress resistance in lower organisms are defined (i.e.

Synthetic libraries of tyrosine-derived bacterial metabolites.

The preparation of a collection of 131 small molecules, reminiscent of families of long chain N-acyl tyrosines, enamides and enol esters that have been isolated from heterologous expression of environmental DNA (eDNA) in Escherichia coli, is reported. The synthetic libraries of N-acyl tyrosines and their 3-keto counterparts were prepared via solid-phase routes, whereas the enamides and enol esters were synthesized in solution-phase.

Preparation of a psammaplysene-based library.

A 28-member focused library, based on the pseudosymmetric template of the marine alkaloids psammaplysenes, was prepared from combinations of components that were, in turn, derived from 4-iodophenol.

Total synthesis of psammaplysenes A and B, naturally occurring inhibitors of FOXO1a nuclear export.

[reaction: see text] Two inhibitors of FOXO1a-mediated nuclear export, psammaplysenes A and B, have been synthesized by a flexible and efficient route. A common starting material, 4-iodophenol, was used to prepare both halves of these pseudosymmetric dibromotyrosine-derived metabolites.