Synthesis and Biological Evaluation of Novel Cationic Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivative for Epidermal Growth Factor Receptor Targeting.

Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization.

Synthesis and Evaluation of Tc(CO) Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging.

The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (Tc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics.

Design, Synthesis, and Biological Evaluations of Novel Thiazolo[4,5-d]pyrimidine Corticotropin Releasing Factor (CRF) Receptor Antagonists as Potential Treatments for Stress Related Disorders and Congenital Adrenal Hyperplasia (CAH).

Corticotropin-releasing factor (CRF) is a key neuropeptide hormone that is secreted from the hypothalamus. It is the master hormone of the HPA axis, which orchestrates the physiological and behavioral responses to stress. Many disorders, including anxiety, depression, addiction relapse, and others, are related to over-activation of this system.

Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice.

Purpose: Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer's ability to target the macrophage mannose receptor CD206.

Methods: First, the uptake of intravenously (i.

Rational Design, Synthesis and Binding Affinity Studies of Anthraquinone Derivatives Conjugated to Gonadotropin-Releasing Hormone (GnRH) Analogues towards Selective Immunosuppression of Hormone-Dependent Cancer.

Gonadotropin-releasing hormone (GnRH) is pivotal in regulating human reproduction and fertility through its specific receptors. Among these, gonadotropin-releasing hormone receptor type I (GnRHR I), which is a member of the G-protein-coupled receptor family, is expressed on the surface of both healthy and malignant cells. Its presence in cancer cells has positioned this receptor as a primary target for the development of novel anti-cancer agents.

Aluminum Fluoride-18 Labeled Mannosylated Dextran: Radiosynthesis and Initial Preclinical Positron Emission Tomography Studies.

Purpose: In addition to being expressed on liver sinusoidal endothelial cells, mannose receptors are also found on antigen-presenting cells, including macrophages, which are mainly involved in the inflammation process. Dextran derivatives of various sizes containing cysteine and mannose moieties have previously been labeled with Tc and used for single-photon emission computed tomography imaging of sentinel lymph nodes. In this study, we radiolabeled 21.

Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents.

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and (+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO) and -[NEt][ReBr(CO)] were used for the preparation of the Re complexes -[Re(NNO)(CO)] () and -[Re(SNO)(CO)] () which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the -[Tc(CO)] core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the -[Tc][Tc(OH)(CO)] precursor.

Synthesis and preclinical evaluation of rhenium and technetium-99m "4 + 1" mixed-ligand complexes bearing quinazoline derivatives as potential EGFR imaging agents.

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (Tc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand Re- and Tc-complexes of the general formula [Tc][Tc(NS)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand.

Synthesis and Characterization of Novel [2 + 1] Tricarbonyl Rhenium Complexes with the Hydrophilic Phosphine Ligands PTA and CAP.

In the pursuit of hydrophilic model -[Re(CO)] complexes for (radio) pharmaceutical applications, six novel [2 + 1] mixed-ligand complexes of the general type -[Re(CO)(bid)P] were synthesized and characterized, where bid is a bidentate ligand bearing either (N, O) or (S, S') donor atom sets and P is the hydrophilic phosphine 1,3,5-triaza-7-phosphoadamantane (PTA) or its macrocyclic homologue 1,4,7-triaza-9-phosphatricyclo[5.3.2.

Biological evaluation of complexes of cyclopentadienyl M(CO) (M = Re, Tc) with high blood-brain barrier penetration potential as brain cancer agents.

To address the major medical need for effective chemotherapeutics/diagnostics for brain cancer, in this work three cyclopentadienyl M(CO) (M = Re, Tc) complexes, which cross the blood-brain barrier (BBB) in high % and are designed to mimic the anticancer agent 2-phenylbenzothiazole, are in vitro and in vivo evaluated for anticancer action. The study includes cytotoxicity and uptake studies in cancer and healthy neuronal cell lines, mechanistic investigation of potential anticancer pathways, and biodistribution studies in mice bearing glioblastoma xenografts. The stable Re complexes exhibit selective uptake and significant antiproliferative effect, particularly against U-251 MG glioblastoma cells, with no significant toxicity in healthy neurons, demonstrating the suitability of this type of complexes to serve as selective therapeutic/imaging agents for brain cancer.

Design, synthesis, structural optimization, SAR, in silico prediction of physicochemical properties and pharmacological evaluation of novel & potent thiazolo[4,5-d]pyrimidine corticotropin releasing factor (CRF) receptor antagonists.

Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide secreted from the hypothalamus and is the main regulator of the hypothalamus-pituitary-adrenocortical (HPA) axis. CRF is the master hormone which modulates physiological and behavioral responses to stress. Many disorders including anxiety, depression, addictive disorders and others are related to over activation of the CRF system.

Effective Labeling of Amine Pharmacophores through the Employment of 2,3-Pyrazinedicarboxylic Anhydride and the Generation of [M(CO)(PyA)P] and -[M(CO)(PyA)P] Complexes (PyA = Pyrazine-2-carboxylate, P = Phosphine, M = Re, Tc).

The -[M(CO)(PyA)(P)] and -[M(CO)(PyA)(P)] neutral complexes (M is Re or Tc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (LH) with [M(CO)] core in water yielded the intermediate -[M(CO)(PyA)(HO)] complexes.

Synthesis and In Vitro Evaluation of Gold Nanoparticles Functionalized with Thiol Ligands for Robust Radiolabeling with Tc.

Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development and in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (Tc) via thiol-bearing ligands attached to the NP surface. More specifically, AuNPs of two different sizes (2 nm and 20 nm, referred to as Au and Au, respectively) were functionalized with two bifunctional thiol ligands (referred to as LH and LH).

Synthesis and evaluation of new mixed "2 + 1" Re, Tc and Re tricarbonyl dithiocarbamate complexes with different monodentate ligands.

A series of "2 + 1" mixed ligand tricarbonyl complexes of the general formula fac-[Re/Tc/Re(CO)(DDTC)(L)] containing diethyldithiocarbamate (DDTC) as a monoanionic bidentate ligand and a series of monodentate ligands L was synthesized, characterized and evaluated. The impact of ligand L on the radiochemical yield (RCY) and biodistribution of the final compounds was also investigated. DDTC and the appropriate L ligand [cyclohexyl isocyanide (cisc), tert-butyl isocyanide (tbi), triphenylphosphine (PPh), methyldiphenylphosphine (PPhMe), triphenylarsine (AsPh), imidazole (im), and 4-aminopyridine (4AP)] readily reacted in equimolar amounts with the [EtN][Re(CO)Br] precursor to afford fac-[Re(CO)(DDTC)(cisc)], Re1, fac-[Re(CO)(DDTC)(tbi)], Re2, fac-[Re(CO)(DDTC)(PPh)], Re3, fac-[Re(CO)(DDTC)(PPhMe)], Re4, fac-[Re(CO)(DDTC)(AsPh)], Re5, fac-[Re(CO)(DDTC)(im)], Re6 and fac-[Re(CO)(DDTC)(4AP)], Re7, complexes in high yields (>80%).

Synthesis, in vitro biological investigation, and molecular dynamics simulations of thiazolopyrimidine based compounds as corticotrophin releasing factor receptor-1 antagonists.

Corticotrophin releasing factor receptor-1 (CRFR1) is a potential target for treatment of depression and anxiety through modifying stress response. A series of new thiazolo[4,5-d]pyrimidine derivatives were designed, prepared and biologically evaluated as potential CRFR1 antagonists. Four compounds produced more than fifty percent inhibition in the [I]-Tyr-sauvagine specific binding assay.

Synthesis, characterization and evaluation of Ga labelled monomeric and dimeric quinazoline derivatives of the HBED-CC chelator targeting the epidermal growth factor receptor.

Tyrosine kinase (TK) receptors including epidermal growth factor receptors (EGFRs) are known to be overexpressed in a wide variety of solid tumors associated with poor prognosis. The HBED-CC chelator N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid 1 was coupled via one or both its propionic acid moieties with the quinazoline EGFR-TK inhibiting pharmacophore 4-amino-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)butanamide 3 resulting in either a monomeric 4 or a dimeric 5 species. Ligands 4 and 5 reacted with Ga generating the corresponding complexes Ga4 and Ga5.

Crystal structure of -aqua-[()-4-(benzo[]thia-zol-2-yl)--(pyridin-2-yl-methyl-idene)aniline-κ ,']tricarbonylrhenium(I) hexa-fluorido-phosphate methanol monosolvate.

In the title compound, -[Re(CHNS)(CO)(HO)]PF·CHOH, the coordination environment of the Re atom is octa-hedral with a CNO coordination set. In this mol-ecule, the ,' bidentate ligand, ()-4-(benzo[]thia-zol-2-yl)--(pyridin-2-yl-methyl-idene)aniline, and the monodentate aqua ligand occupy the three available coordination sites of the [Re(CO)] core, generating a '2 + 1' mixed-ligand complex. In this complex, the Re-C bonds of the carbonyl ligands to the coordinating ,' atoms of the bidentate ligand are longer than the Re-C bond of the carbonyl group to the aqua ligand, in accordance with the intensity of their effects.

Remarkable Brain Penetration of Cyclopentadienyl M(CO) (M = Tc, Re) Derivatives of Benzothiazole and Benzimidazole Paves the Way for Their Application as Diagnostic, with Single-Photon-Emission Computed Tomography (SPECT), and Therapeutic Agents for Alzheimer's Disease.

The synthesis and evaluation of three novel Tc complexes (Tc-1-3) and their corresponding Re complexes (Re-1-3), in which the phenyl ring of 2-phenylbenzothiazole or 2-phenylbenzimidazole is replaced by the cyclopentadienyl tricarbonyl [CpTc(CO)] core, are reported. Both Tc and Re complexes were prepared from the corresponding ferrocenyl derivatives, and the Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. The complexes exhibit effective in vitro binding to β-amyloid (Aβ) plaques and fibrils, inhibit Aβ fibril formation, and significantly reduce Aβ-induced cytotoxicity and reactive oxygen species production in neuronal cell cultures.

Simultaneous determination of paraquat and atrazine in water samples with a white light reflectance spectroscopy biosensor.

An optical immunosensor based on White Light Reflectance Spectroscopy for the simultaneous determination of the herbicides atrazine and paraquat in drinking water samples is demonstrated. The biosensor allows for the label-free real-time monitoring of biomolecular interactions taking place onto a SiO/Si chip by transforming the shift in the reflected interference spectrum due to reaction to effective biomolecular layer thickness. Dual-analyte determination is accomplished by functionalizing spatially distinct areas of the chip with protein conjugates of the two herbicides and scanning the surface with an optical reflection probe.

Dicarbonyl cis-[M(CO)(N,O)(C)(P)] (M = Re, Tc) Complexes with a New [2 + 1 + 1] Donor Atom Combination.

The synthesis and characterization of the dicarbonyl mixed ligand cis-[Re(CO)(quin)(cisc)(PPh)] complex, 4, where quin is the deprotonated quinaldic acid, cisc is cyclohexyl isocyanide, and PPh is triphenylphosphine, is presented. The synthesis of 4 proceeds in three steps. In the first, the intermediate fac-[Re(CO)(quin)(HO)] aqua complex 2 is generated from the fac-[NEt][Re(CO)Br] precursor, together with the brominated products fac-[Re(CO)(quinH)(Br)] 1a and fac-[NEt][Re(CO)(quin)(Br)] 1b, in low yield.

Synthesis and evaluation of Tc/Re-tricarbonyl complexes of the triphenylphosphonium cation for mitochondrial targeting.

Introduction: Lipophilic delocalized cations accumulate in tumor cell mitochondria due to their higher transmembrane potential. In this work, this strategy was adopted for the development of Tc tumor-targeted imaging agents.

Methods: Two tridentate ligands containing the triphenylphosphonium cation, L1 (S-cysteinyl) and L2 (N-iminodiacetate) as well as the respective Tc/ReL1 and Tc/ReL2 tricarbonyl complexes were synthesized.

2-(4'-Aminophenyl)benzothiazole Labeled with Tc-Cyclopentadienyl for Imaging β-Amyloid Plaques.

The development of a Tc-radiotracer for imaging of β-amyloid (Aβ) plaques with single photon emission computed tomography (SPECT) is strongly anticipated to provide a low cost and broadly accessible diagnostic tool for Alzheimer's disease (AD). Within this framework, 2-(4'-aminophenyl)benzothiazole, known to display affinity and specificity for Aβ plaques, has been joined to the tricarbonyl -[M(CO)] (M = Re(I), Tc(I)) core through the cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes ( and , respectively). The complex was completely characterized with spectroscopic methods and was shown to selectively stain Aβ plaques on sections of human AD brain tissue.

Rhenium(I) Tricarbonyl Complexes with (2-Hydroxyphenyl)diphenylphosphine as PO Bidentate Ligand.

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)LL] complexes (M = Re, Tc) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand (LH) and a series of monodentate ligands (L). First, fac-[Re(CO)(PO)(HO)], 1, was synthesized by reaction of POH and [EtN][Re(CO)Br] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand.