Search Results (161)

Studies of natural products and their semisynthetic derivatives are a valuable source of therapeutic agents. The aim of this work was to obtain new 30-phosphoramidate derivatives of betulin and determine their biological potential. The synthetic approach utilized the Staudinger reaction (the introduction of a phosphoramidate group), the Steglich reaction (the introduction of an alkynyl group), and the Jones reaction (the introduction of a carboxyl group). The structures of the target compounds were determined using spectroscopic methods (¹H NMR, ¹³C NMR, ³¹P NMR, and HRMS). The new derivatives were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, and HCT116 cancer cells and against normal MCF-10A cells using the MTT and SRB methods. Apoptosis studies were performed for the most active compounds (6B and 7A), potential molecular targets (AutoDock software) were identified, and lipophilicity parameters (RP-TLC method, SwissADME website) were determined. The greatest effect on apoptosis and caspase 3/7 activation was observed for the diester derivative 7A. Compound 7A showed a high lipophilicity parameter in the study group. Full article

Nature-inspired ligands, including natural product scaffolds and bio-inspired motifs, have emerged as an important source for the development of gold(I) complexes with promising preclinical anticancer activity. This review focuses on structurally characterised gold(I) complexes derived from these ligands, emphasising how ligand structure and gold coordination influence the biological activity. This paper covers the synthesis of nature-inspired gold(I) complexes, alkynyl, N-heterocyclic carbene (NHC), heteroatom-donor, and heterobimetallic complexes, which collectively contribute to enhanced cytotoxicity, stability, and mechanistic diversity. By focusing on these nature-inspired gold(I) complexes, this review provides a concise structure–activity perspective and outlines future opportunities for rational design in anticancer research. Full article

The epidermal growth factor receptor (EGFR) is a highly attractive and promising target for novel anticancer agents, particularly for non-small-cell lung cancer (NSCLC), due to its crucial role in regulating cell survival and proliferation. Despite the development of first-generation reversible inhibitors like Gefitinib and Erlotinib, acquired resistance necessitated the discovery of highly potent irreversible inhibitors effective against drug-resistant mutants. Molecular docking calculations utilizing both EGFR conformations identified five top-ranked compounds (QN012, QN017, QN019, QN022, and QN023) proposed for synthesis and biological evaluation. These in silico studies predicted high inhibitory activity against the active and inactive state of EGFR. Herein, we report the design, synthesis and biological evaluation of novel 4-anilino quinazoline derivatives, bearing various alkynyl substituents at position 6, expected to bind to the hinge Met793 residue of EGFR. The effects of the derivatives on various cancer cell lines in terms of cytotoxic/cytostatic activity, interference with cell cycle phase distribution, and suppression of EGFR phosphorylation set the basis for the design of more potent derivatives. Full article

We report the use of σ-alkynyl d⁶ electron-rich transition metal complexes as electron-releasing end-groups in octupolar molecules designed for nonlinear optical (NLO) applications, specifically, N,N′,N″-triarylisocyanurates (5,7,8,10,12) and 1,3,5-triarylbenzenes (6,9,11) functionalized by Fe(II) and Ru(II) organometallic moieties, and their NLO properties, as assessed by hyper-Rayleigh scattering (HRS) and Z-scan. The redox properties are briefly investigated through isolation of the corresponding Fe(III) trications 5[PF₆]₃ and 6[PF₆]₃. The second-harmonic generation (SHG) or two-photon absorption (2PA) performance of the Fe(II) and Ru(II) parents is compared with the help of TD-DFT calculations performed on models. Comparison with tris-ferrocenyl isocyanurate 4 reveals that the σ-connection of the metallic centers to the π-manifold is superior to the η⁵-connection for enhancing NLO properties. The positive effect of organometallic end-groups on NLO properties relative to purely organic electron-releasing substituents is established. The mechanism by which NLO enhancement occurs is complex and possibly connected to the polarizable π-electrons in the ligands surrounding the metal alkynyl units, but in most cases, the observed NLO enhancement must arise from the transition metal centers interacting with the central π-manifold. Full article

Methylbutynol (MB) is a typical propargylic alcohol with both alkynyl and hydroxyl groups, featuring excellent modifiability and broad applications. Currently, it is produced through the reaction of alkaline metallic acetylides and acetone, requiring expensive raw material and harsh reaction conditions. Herein, a novel method was proposed by replacing the metallic acetylide with calcium carbide (CaC₂) as a low-cost industrial acetylide reagent. The effects of solvent, activator, and proton donor on the ball mill reaction, and the defoaming performance of the resultant MB and its oxidative coupling product (2,7-dimethyl-3,5-octadiyn-2,7-diol), were studied. Nucleophilic reactivity of CaC₂ with acetone can be regulated by the activating effect of the ball mill, an appropriate activator, and a proton donor. High yield of MB (~94%) was obtained under synergistic action of TBAF·3H₂O and acetylene, which represents a facile synthesis process of MB under mild conditions. MB exhibits good defoaming performance, and 2,7-dimethyl-3,5-octadiyn-2,7-diol is more promising, being an excellent non-ionic defoamer. The result is of great significance for exploring new chemical reactions of CaC₂ and its high-value utilizations. Full article

The microwave-aided racemic synthesis of six 5-hydroxy-5-vinyl-2-cyclopentenone-type natural products was achieved. A key reaction involving the construction of the α-keto vinyl carbinol function was realized by applying a Mislow–Evans rearrangement of an allylic sulfoxide, which was prepared by conjugate addition of cyclopentane-1,3-dione-derived enolate to alkynyl sulfoxide to afford 5-hydroxy-3-methoxy-5-vinyl-2-cyclopentenone (1). From the common intermediate 1, five other congeneric natural products were synthesized. Full article

Herein, we report a cobalt-catalyzed cross-coupling of organoselenides with Grignard reagents using simple CoCl₂ as the catalyst. This efficient method accommodates a broad scope of selenides, including vinyl, aryl, heteroaryl, and alkynyl derivatives, under mild and ligand-free conditions. Remarkably, the reaction proceeds efficiently without additives and afforded the desired products in moderate to good yields within just 3 h. Full article

Background/Objectives: The role of α-synuclein (α-syn) in the pathogenesis of Parkinson’s disease (PD) or neurodegenerative diseases such as Lewy body dementia (LBD) and multiple system atrophy (MSA) is commonly accepted. Through different physiological dysfunctions, abnormal forms of α-syn are generated. These abnormal aggregates accumulate and alter pre- and postsynaptic transmission, in particular that of dopamine. Thus, the development of a diagnostic biomarker of synucleinopathies remains crucial and challenging. The development of an α-syn positron emission tomography (PET) radiopharmaceutical may be suitable to early diagnose and stratify patients, follow up disease progression, and evaluate future therapies. Methods: To develop a selective α-syn PET tracer, we synthesized an original series based on alkynyl(aza)indoles. Fifteen final ligands were synthesized bearing indoles or azaindoles from one side of the alkyne and a substituted phenyl ring for the opposite side of the alkyne. The final ligands were tested to determine Ki and/or Kd toward α-syn, tau, and Aβ. Results: The SAR showed that the indole series exhibited moderate to low affinity for α-syn and, moreover, lower Ki toward Aβ and tau (i.e., compound 39, Ki_(αsyn) 21.7 nM, Ki_(Aβ) 64.4 nM, Ki_(Tau) 27.6 nM), highlighting the low potency of these series to afford an α-syn tracer. The introduction of a nitrogen on the different positions of the phenyl to obtain the corresponding azaindoles resulted for most of the compounds in better affinity for α-syn and selectivity towards Aβ compared to the indole analogs (i.e., compound 43, Ki_(αsyn) 4.7 nM, Ki_(Aβ) 24.4 nM, and Ki_(Tau) 4.61 nM). A fluorinated azaindole derivative was prepared with a view to obtaining a ¹⁸F tracer and exhibited the highest affinity for α-syn but without selectivity against tau and Aβ. The radiosynthesis of [¹⁸F]45 was performed in a two-step procedure starting from the tosylated and protected precursor. [¹⁸F]45 was obtained in 85 ± 5 min with a radiochemical yield of 32 ± 3%. Molar activity, determined from a calibration with stable 45, was around 130 GBq/µmole. The dynamic PET imaging showed that [¹⁸F]45 was able to cross the blood–brain barrier, but non-specific uptake was observed, confirming the in vitro results. Conclusions: Although promising nanomolar affinity for the target, the new tracer showed mainly non-specific in vivo uptake in the rat brain, indicating that further pharmacomodulations on the azaindole series are required. Full article

Chiral coordination compounds are of growing interest due to their structural diversity and wide applicability. Besides chirality, alcohol and especially oxime-functionalized limonene derivatives confer water solubility, stability, and the appropriate reactivity to enable their use in asymmetric catalysis—such as allylic substitution, alkynylation, transfer hydrogenation, and selective C–C bond formation. Biologically, they have shown promising anticancer, antibacterial, and antibiofilm activity. This review presents an integrated overview of the synthesis, properties, and applications of chiral transition metal complexes featuring ligands derived from inexpensive, naturally occurring R- and S-limonene substrates, and explore their roles in catalysis and biological activity. Full article

Molecules provide the smallest possible circuits in which quantum interference and electron correlation can be engineered to perform logical operations, including the universal NAND gate. We investigate a chemically encoded quantum NAND tree based on alkynyl-extended iso-polyacetylene backbones, where inputs are set by end-group substitution and outputs are read from the presence or absence of transmission nodes. Using quantum many-body transport theory, we show that NAND behavior persists in the presence of dynamic correlations, but that the nodal positions and their chemical shifts depend sensitively on electron–electron interactions. This sensitivity highlights the potential of these systems not only to probe the strength of electronic correlations but also to harness them in shaping logical response. The thermopower is identified as a chemically robust readout of gate logic, providing discrimination margins that greatly exceed typical experimental uncertainties, in an observable governed primarily by the variation of transport rather than its absolute magnitude. Full article

In the present work we investigate by first principles calculations the structural, electronic, and optical properties of alkyl, 1-alkenyl and 1-alkynyl C₈ moieties chemisorbed on hydrogen-terminated silicon nanowire oriented along the ⟨112⟩ direction. Our results disclose how the nature of the carbon–carbon bond contiguous to the Si surface influences the behavior of the system. While 1-alkynyl groups exhibit the strongest Si–C bonding, it is 1-alkenyl functionalization that induces the most significant enhancement in optical absorption within the visible range due to charge transfer. The charge transferred from the nanowire to the moiety confirms the electronic coupling of the two systems. We found that the highest occupied molecular orbital of the 1-alkenyl moiety lies only 0.3 eV below the valence band edge of the hydrogen-terminated silicon nanowire, enabling new low-energy optical transitions which are absent in both the unmodified silicon nanowire and the isolated molecule. These findings demonstrate a synergistic effect of functionalization. Our study provides valuable insights into the design of functionalized silicon nanostructures with tailored optical properties, with potential implications for applications in sensing, photonics, and energy conversion. Full article

Background/Objectives: RMC-113, a 3-alkynyl-6-aryl-disubstituted isothiazolo[4,3-b]pyridine, is a dual inhibitor of the lipid kinases PIKfyve and PIP4K2C with broad-spectrum antiviral activity. The aim was to study the structure–activity relationship (SAR) of isothiazolo[4,3-b]pyridines as dual PIKfyve/PIP4K2C inhibitors. Methods: A series of isothiazolo[4,3-b]pyridines was synthesized by introducing structural variety at positions 3 and 6 of the central scaffold. The primary assay to guide the synthetic chemistry was a biochemical PIKfyve assay, with a number of analogues also tested for PIP4K2C binding affinity. Finally, isothiazolo[4,3-b]pyridines were also evaluated for antiviral and antitumoral activity in cell-based assays. Results: PIKfyve inhibition tolerated a wide variety of substituents on the aryl ring at position 6 of the isothiazolo[4,3-b]pyridine scaffold, with the 4-carboxamide analogue emerging as the most potent (IC₅₀ = 1 nM). The SAR at position 3 was more restricted, although the introduction of electron-donating groups (such as a methyl and methoxy) on the pyridinyl ring yielded potent PIKfyve inhibitors, with IC₅₀ values in the low nM range. The acetylenic moiety was essential for PIKfyve inhibition, and only the saturated ethyl linker displayed potent PIKfyve inhibition, albeit less active than the acetylene counterpart. The compounds were 2- to 5-fold less potent on PIP4K2C relative to PIKfyve. These dual PIKfyve/PIP4K2C inhibitors displayed antiviral activity against both the venezuelan equine encephalitis virus (VEEV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A screening against a panel of cancer cell lines revealed antitumoral activity, although some of the potent PIKfyve/PIP5K2C inhibitors lacked antitumoral activity. Conclusions: Isothiazolo[4,3-b]pyridines are dual PIKfyve/PIP4K2C inhibitors displaying broad-spectrum antiviral, as well as antitumoral, activity. Full article

γ-Glutamyl transpeptidase (GGT) is overexpressed in a variety of diseases, making it an important diagnostic criterion for diseases. Herein, a new fluorescence probe based on naphthalimide (Glu-MDA) was developed and employed for the rapid detection of GGT in tumor cells or samples. Alkynylated naphthalimide is the fluorescent core for excellent fluorescence response. The covalent bridging of self-immolative short linkers reduces the steric hindrance between probes and enzyme cleavage sites, which leads to improved enzymatic reaction kinetics. Glu-MDA shows a rapid response and excellent selectivity with a detection limit of 0.044 U/L. This allows the efficient detection of GGT levels in solution and cells. Simultaneously, the construction of Glu-MDA pre-stained test strips provided an innovative strategy for the qualitative detection of GGT activity, helping to detect GGT faster, more portably, and cost-effectively in various scenarios. Full article

Herein, we report a one-pot palladium- and ligand-free tandem Sonogashira coupling/regioselective 6-endo-dig oxacyclization reaction of 2,4-diiodo-1-methyl-imidazole-5-carboxylic acid with terminal alkynes mediated by Copper(I). This impressive approach offers a straightforward, practical, and efficient tandem procedure for accessing 2-alkynylated pyrano[4,3-d]imidazol-4-one in moderate to good yields with an exclusive 6-endo-dig oxacyclization. Notably, this cost-effective methodology demonstrates broad substrate compatibility with various commercially available aliphatic and (hetero)aromatic terminal alkynes. Furthermore, DFT studies were performed to elucidate the origin of this regioselective 6-endo-dig oxacyclization reaction. Full article

Mechanochemical and transition-metal-catalyzed reactions of alkynes, exhibiting significant advantages like short reaction time, solvent-free, high yield and good selectivity, were considered to be green and sustainable pathways to access functionalized molecules and obtained increasing attention due to the superiorities of mechanochemical processes and the reactivities of alkynes. The ball milling and CuI-catalyzed Sonogashira coupling of alkyne and aryl iodide avoided the use of common palladium catalysts. The mechanochemical Rh(III)- and Au(I)-catalyzed C–H alkynylations of indoles formed the 2-alkynylated and 3-alkynylated indoles selectively. The mechanochemical and copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynes and azides were developed to synthesize 1,2,3-triazoles. Isoxazole could be formed through ball-milling-enabled and Ru-promoted cycloaddition of alkyne and hydroxyimidel chloride. In this review, the generation of mechanochemical and transition-metal-catalyzed reactions of alkynes was highlighted. Firstly, the superiority and application of transition-metal-catalyzed reactions of alkynes were briefly introduced. After presenting the usefulness of green chemistry and mechanochemical reactions, mechanochemical and transition-metal-catalyzed reactions of alkynes were classified and demonstrated in detail. Based on different kinds of reactions of alkynes, mechanochemical and transition-metal-catalyzed coupling, cycloaddition and alkenylation reactions were summarized and the proposed reaction mechanisms were disclosed if available. Full article