Synthesis, characterization and bioactivity of new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives.

Pyridone heterocycles, such as furo[2,3-b]pyridines, have emerged as prominent scaffolds in medicinal chemistry due to their versatile pharmacological properties, including significant anticancer activity. In this study, we successfully synthesized new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives from chalcones bearing 4-(benzyloxy)phenyl and dichlorothiophenyl subunits to explore their therapeutic potential against breast cancer. By employing a synthetic strategy involving Claisen-Schmidt condensation followed by sequential cyclizations and functional modifications, we synthesized and characterized four compounds (MI-S0, MI-S1, MI-S2, and MI-S3) using various spectroscopic methods, including FT-IR, 1H-NMR, 13C-NMR, DEPT, H,H- and C,H-COSY, and HRMS. The in vitro cytotoxic activity of these compounds was evaluated against two breast cancer cell lines, MCF-7 and MDA-MB-231, and compared with a noncancerous breast cell line, MCF-10A. All compounds exhibited potent cytotoxic activities with minimal selectivity toward normal cells. Molecular docking studies targeting the serine/threonine kinase AKT1, estrogen receptor alpha (ERα), and human epidermal growth factor receptor 2 (HER2) revealed strong binding affinities, suggesting a mechanism involving the disruption of key cellular signaling pathways. These findings underscore the potential of furo[2,3-b]pyridine derivatives as promising candidates for further development into anticancer agents, laying the groundwork for future investigations into their selective therapeutic efficacy and molecular mechanisms of action.

Selective uranyl ion-imprinting with clickable amidoxime-functionalized pullulan.

Manufacturing a highly effective sorbent for removing UO22+ ions from aqueous effluents is vital for safeguarding the environment and recovering valuable resources. This research presents an innovative strategy employing adsorbents derived from pullulan, specifically tailored with furfuryl-amidoxime (FAO), to improve their affinity for UO22+ ions. The formation of a UO22+ ion-imprinted sorbent (U-II-P) was achieved by crosslinking the UO22+/FAO-modified pullulan (FAO-P) complex with bis(maleimido)ethane (BME) via click Diels-Alder (DA) cyclization, enhancing its attraction and specificity for UO22+ ions. Detailed characterization of the synthesis was performed using NMR and FTIR spectroscopy, and the sorbent's external textures were analyzed using scanning electron microscopy (SEM). The U-II-P sorbent showcased outstanding preference for UO22+ over other metallic ions, with the most efficient adsorption occurring at pH 5. It exhibited a significant adsorption capacity of 262 mg/g, closely aligning with the predictions of the Langmuir adsorption model and obeying pseudo-second-order kinetic behavior. This investigation underlines the effectiveness of FAO-P as a specialized solution for UO22+ ion extraction from wastewater, positioning it as a viable option for the remediation of heavy metals.

The Synthesis, Characterization, Cytotoxic Activity Assessment and Structure-Activity Relationship of 4-Aryl-6-(2,5-dichlorothiophen-3-yl)-2-methoxypyridine-3-carbonitriles.

A series of 2-methoxypyridine-3-carbonitrile (5a-i)-bearing aryl substituents were successfully synthesized in good yields by the condensation of chalcones (4a-i) with malononitrile in basic medium. The condensation process, in most cases, offers a route to a variety of methoxypyridine derivatives (6a-g) as side products in poor yields. All new compounds were fully characterized using different spectroscopic methods. Mass ESI-HMRS measurements were also performed. Furthermore, these compounds were screened for their in vitro cytotoxicity activities against three cancer cell lines; namely, those of the liver (line HepG2), prostate (line DU145) and breast (line MBA-MB-231). The cytotoxicity assessment revealed that compounds 5d, 5g, 5h and 5i exhibit promising antiproliferative effects (IC50 1-5 µM) against those three cancer cell lines.

Synthesis of Fluorescent 1-(3-Amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one: Crystal Structure, Fluorescence Behavior, Antimicrobial and Antioxidant Studies.

Furopyridine III, namely 1-(3-amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one, synthesized from 4-(4-(tert-butyl)phenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile I in two steps. The title compound is characterized by NMR, MS and its X-ray structure. The molecular structure consists of planar furopyridine ring with both phenyl rings being inclined from the furopyridine scaffold to a significant different extent. There are three intramolecular hydrogen bonds within the structure. The lattice is stabilized by N-H…O, H2C-H …π and π…π intermolecular interactions leading to three-dimensional network. Compound III exhibits fluorescent properties, which are investigated. Antimicrobial potential and antioxidant activity screening studies for the title compound III and the heterocyclic derivatives, I and II, show no activity towards neither bacterial nor fungal strains, while they exhibited weak to moderate antioxidant activity compared to reference.

Clear Cell Renal Cell Carcinoma is linked to Epithelial-to-Mesenchymal Transition and to Fibrosis.

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq® Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC Gene expression analysis showed augmented abundance of AXL and MMP14, as well as down-regulated expression of KL (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets MMP14 and AXL Survival analysis based on a subset of genes from our list EMT-related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions.

Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus, and Leukemia Cells.

Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline-artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline-artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but at the same time more active than the clinically used drugs dihydroartemisinin (EC50 = 2.4 nM) and chloroquine (EC50 = 9.8 nM). Furthermore, hybrids 9 and 10 were the most potent compounds with regard to anticytomegaloviral activity (EC50 = 0.15-0.21 µM). They were able to outperform ganciclovir (EC50 = 2.6 µM), which is the relevant standard drug of antiviral therapy, by a factor of 12-17. Moreover, we identified a new highly active quinazoline derivative, compound 14, that is most effective in suppressing cytomegalovirus replication with an EC50 value in the nanomolar range (EC50 = 50 nM). In addition, hybrid 9 exhibited an antileukemia effect similar to that of artesunic acid, with EC50 values in the low micromolar range, and was 45 times more active toward the multidrug-resistant CEM/ADR5000 cells (EC50 = 0.5 µM) than the standard drug doxorubicin.

Synthesis, Spectral Characterization and Fluorescent Assessment of 1,3,5-Triaryl-2-pyrazoline Derivatives: Experimental and Theoretical Studies.

Two new pyrazoline derivatives, namely 5-(4-bromophenyl)-3-(5-chlorothiophen-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazole (3) and 5-(4-bromophenyl)-3-(2,5-dichlorothiophen-3-yl)-1-phenyl-4,5-dihydro-1H-pyrazole (4) have been synthesized and characterized based on their spectral (IR, (1)H and (13)C NMR and MS) data and microanalysis. The fluorescence properties of 3 and 4 were studied by UV-Vis and emission spectroscopy. For compound 3, a fluorescence emission was observed in the blue region of the visible spectrum. The effect of different solvents on fluorescence was also investigated. Density Functional Theory calculations have also been performed to gain insight into geometric, electronic and spectroscopic properties of the pyrazoline derivatives. Both structures are analysed and compared in order to rationalize the different behaviour in 3 and 4.

3-Methyl-amino-3-phenyl-propan-1-ol.

The title compound, C(10)H(15)NO, is an amino alcohol with the hy-droxy group residing on the terminal C atom. Apart from the hy-droxy group and the phenyl ring, all non-H atoms are almost coplanar. In the crystal, classical O-H⋯N and N-H⋯O hydrogen bonds connect the mol-ecules into centrosymmetric dimers [R(2) (2)(12) descriptor] and tetra-meric units [R(4) (4)(8) descriptor] as ring motifs, consolidating a three-dimensional network.

1,4-Dihydroxy-quinoxaline-2,3(1H,4H)-dione.

The asymmetric unit of the title compound, C(8)H(6)N(2)O(4), contains one half-mol-ecule; a twofold rotation axis bisects the molecule. The quinoxaline ring is planar, which can be attributed to electron delocalization. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into R(2) (2)(10) motifs, leading to layers, which inter-act via phen-yl-phenyl inter-actions (C⋯C distances in the range 3.238-3.521 Å).