Gold nanoclusters AuAcCys normalize intracellular ROS without increasing cytoplasmic alarmin acHMGB1 abundance in human microglia and neurons.

This study focuses on the modulatory effects of gold nanoclusters with 25 gold atoms and 18 acetyl cysteines (AuAcCys) in human microglia, human iPSC-derived neurons and SH-SY5Y differentiated human neuronal cells. The combination of chemical, biological, and computational methods shows the well-retained viability of these human cells treated with AuAcCys, interactions between AuAcCys and transcription factor TFEB (computational approach), interactions between TFEB and HMGB1 (proximity ligation assay and molecular modeling using AlphaFold), modulation of the abundance and location of acHMGB1 by AuAcCys (immunocytochemistry), and the reduction of ROS in cells treated with AuAcCys (CellROX live imaging). These novel findings in human neural cells, particularly neurons, encourage further studies in experimental animal models of neurological disorders and/or human organoids to exploit the unique structural and photophysical properties of gold nanoclusters and to better understand their ability to modulate molecular mechanisms in human cells.

Novel PLGA-based nanoformulation decreases doxorubicin-induced cardiotoxicity.

Nanotechnology has the potential to provide formulations of antitumor agents with increased selectivity towards cancer tissue thereby decreasing systemic toxicity. This study evaluated the potential of novel nanoformulation based on poly(lactic--glycolic acid) (PLGA) to reduce the cardiotoxic potential of doxorubicin (DOX). toxicity of PLGADOX was compared with clinically approved non-PEGylated, liposomal nanoformulation of DOX (LipoDOX) and conventional DOX form (ConvDOX).

Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors.

Inhibiting quorum sensing (QS), a central communication system, is a promising strategy to combat bacterial pathogens without antibiotics. Here, we designed novel hybrid compounds targeting the PQS ( quinolone signal)-dependent quorum sensing (QS) of that is one of the multidrug-resistant and highly virulent pathogens with urgent need of new antibacterial strategies. We synthesized 12 compounds using standard procedures to combine halogen-substituted anthranilic acids with 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline, linked via 1,3,4-oxadiazole.

Anthranilamides with quinoline and β-carboline scaffolds: design, synthesis, and biological activity.

In the present study, we report the design and synthesis of novel amide-type hybrid molecules based on anthranilic acid and quinoline or β-carboline heterocyclic scaffolds. Three types of biological screenings were performed: (i) in vitro antiproliferative screening against a panel of solid tumor and leukemia cell lines, (ii) antiviral screening against several RNA viruses, and (iii) anti-quorum sensing screening using gram-negative Chromobacterium violaceum as the reporter strain. Antiproliferative screening revealed a high activity of several compounds.

Synthesis and Biological Evaluation of Harmirins, Novel Harmine-Coumarin Hybrids as Potential Anticancer Agents.

As cancer remains one of the major health burdens worldwide, novel agents, due to the development of resistance, are needed. In this work, we designed and synthesized harmirins, which are hybrid compounds comprising harmine and coumarin scaffolds, evaluated their antiproliferative activity, and conducted cell localization and cell cycle analysis experiments. Harmirins were prepared from the corresponding alkynes and azides under mild reaction conditions using Cu(I) catalyzed azide-alkyne cycloaddition, leading to the formation of the 1-1,2,3-triazole ring.

Mass spectrometry imaging in zebrafish larvae for assessing drug safety and metabolism.

Drug safety assessment in the early phases of drug discovery is critical to facilitate the rapid development of novel therapeutics. Recently, teleost zebrafish (Danio rerio) has emerged as a promising vertebrate model for the assessment of drug safety. Zebrafish is a convenient model because of its small size, high fecundity, embryo transparency, and ex utero development.

Itaconic acid hybrids as potential anticancer agents.

In this paper, we report the synthesis of novel hybrids 2-14 based on itaconic acid and fluoroaniline, pyridine, indole and quinoline scaffolds. Itaconic acid is a naturally occurring compound with a Michael acceptor moiety, a key structural feature in several anticancer and antiviral drugs, responsible for the covalent binding of a drug to the cysteine residue of a specific protein. Aromatic parts of the hybrids also come from the substances reported as anticancer or antiviral agents.

Chloroquine fumardiamides as novel quorum sensing inhibitors.

Quorum sensing inhibitors (QSIs) that specifically interfere with bacterial cell-to-cell communication are considered as an alternative approach to conventional antibacterial therapy. In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-negative Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-negative, mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides.

Primaquine and Chloroquine Fumardiamides as Promising Antiplasmodial Agents.

This paper describes a continuation of our efforts in the pursuit of novel antiplasmodial agents with optimized properties. Following our previous discovery of biologically potent asymmetric primaquine (PQ) and halogenaniline fumardiamides (-), we now report their significant in vitro activity against the hepatic stages of parasites. Furthermore, we successfully prepared chloroquine (CQ) analogue derivatives (-) and evaluated their activity against both the hepatic and erythrocytic stages of .

Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides.

The paper is focused on the synthesis and screening of the antiplasmodial activity of novel fumardiamides 5-10 with the mefloquine pharmacophore and a Michael acceptor motif. Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (E)-ethyl 4-chloro-4-oxobut-2-enoate (1) and N1-(2,8-bis(trifluoromethyl)quinolin-4-yl) butane-1,4-diamine (2).

Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action of a novel hydroxamic acid hybrid molecule.

Glioblastoma multiforme is one of the most aggressive brain tumors and current therapies with temozolomide or suberoylanilide hydroxamic acid (SAHA, vorinostat) show considerable limitations. SAHA is a histone deacetylase (HDAC) inhibitor that can cause undesirable side effects due to the lack of selectivity. We show here properties of a novel hybrid molecule, sahaquine, which selectively inhibits cytoplasmic HDAC6 at nanomolar concentrations without markedly suppressing class I HDACs.

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents.

We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding.

Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors.

Novel primaquine (PQ) and halogenaniline asymmetric fumardiamides ⁻, potential Michael acceptors, and their reduced analogues succindiamides ⁻ were prepared by simple three-step reactions: coupling reaction between PQ and mono-ethyl fumarate () or mono-methyl succinate (), hydrolysis of PQ-dicarboxylic acid mono-ester conjugates , to corresponding acids ,, and a coupling reaction with halogenanilines. 1-[bis(Dimethylamino)methylene]-1-1,2,3-triazolo[4,5-]pyridinium 3-oxide hexafluorophosphate (HATU) was used as a coupling reagent along with Hünig's base. Compounds and were evaluated against a panel of bacteria, several strains, fungi, a set of viruses, and nine different human tumor cell lines.