Journal of Heterocyclic Chemistry最新文献

A straightforward one-pot synthesis of novel trisubstituted methanes (TRSMs) has been attained through a three-component reaction involving 4-hydroxybenzo[h]quinolin-2(1H)-one, 4-amino-2H-chromen-2-one, and various aldehyde derivatives, using p-TSA. p-Toluene sulfonic acid (p-TSA), a non-toxic, cost-effective, easily accessible, and environmentally friendly organic acid catalyst, was investigated for its ability to mediate this reaction. The salient features of this protocol are: good to excellent yields of products (84%–92%), short reaction times, excellent compatibility with various functional groups, and a cost-effective catalyst that eliminates the need for column chromatography. Furthermore, these TRSMs are expected to make significant contributions as highly valuable compounds in drug design and the development of novel therapies, owing to their broad and diverse biologically active moieties. The structures of these newly synthesized TRSMs were determined using IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis.

Among saturated fused bicyclic nitrogen heterocycles, decahydroquinolines (DHQs) represent a unique structural moiety for the development of novel therapeutic agents, primarily owing to the rich stereochemical diversity inherent in these frameworks. The therapeutic activities of DHQ derivatives are influenced by the bicycle system's fusion mode and substituent spatial orientation. The development of different synthetic routes to DHQs and their analogues has been done to investigate the influence of their three-dimensional structure on physiological effects and to uncover the conformational and configurational intricacies of these compounds. This review covers the majority of the methods that have been used to synthesize a wide variety of synthetic DHQs and natural DHQ-containing alkaloids. Furthermore, it presents a review of their reported biological functions, which include local anesthetic, analgesic, antiarrhythmic, anti-inflammatory, anticholinergic, spasmolytic, antifungal, and antiviral properties, as well as other properties.

In this study, we have developed new hybrid compounds by connecting bis-heterocycles with a 2,3-diphenoxyquinoxaline core. This is performed by combining 4,4′-(quinoxaline-2,3-diylbis(oxy))dibenzaldehyde with the necessary reagents via Hantzsch and Biginelli reactions. The newly synthesized compounds' structures are determined by elemental analysis, ¹H NMR, ¹³C NMR, IR, and MS spectra. The tested compound 18 has the strongest antibacterial activities against S. aureus and E. coli, with inhibition zones of 18 and 14.67 mm, respectively. The tested compound 5 exhibited the strongest antibacterial activities against S. aureus, with an inhibition zone of 17 mm. Molecular docking studies of the most efficient compounds were performed against two proteins, including ATP-dependent Clp protease ATP-binding subunit ClpA (UniProt ID: P0ABH9) and Glycerol dehydrogenase (GDH) (UniProt ID: P0A9S5). Compound 5 interacted with the ClpA active site, exhibiting a binding score of ∆G = −9.2 Kcal/mol, while 18 interacted with the GDH active site, exhibiting a binding score of ∆G = −11.4 Kcal/mol.

In this study, five novel flavone-sulfonamide derivatives (h1–h5) were designed and synthesized based on the pharmacologically active scaffolds of flavones and sulfonamides. The structures of the compounds were characterized by ¹H/¹³C NMR, HRMS, and melting point analysis. In vitro antiproliferative activity was evaluated against human cervical cancer cells (HeLa), murine melanoma cells (B16F10), and human hepatocellular carcinoma cells (HepG2). Among them, compound h5 exhibited the most potent activity against HeLa cells, with an IC₅₀ value of 1.85 μM. Confocal laser scanning microscopy and flow cytometry analyses indicated that h5 induced early apoptosis and caused cell cycle arrest at the S and G2/M phases in HeLa cells. Network pharmacology analysis suggested that h5 might exert its antitumor effects by modulating the PI3K/Akt signaling pathway, with PIK3CA, PIK3CB, and PIK3CD identified as potential targets. Molecular docking and 100 ns molecular dynamics simulations were performed to investigate the binding stability of h5 with PI3K isoforms, and RMSD, RMSF, and Rg analyses supported the structural stability of the complexes. Furthermore, density functional theory (DFT) calculations revealed the frontier molecular orbitals and electrostatic potential distributions of h5, indicating that the flavone core and sulfonamide moiety may serve as key reactive sites. These findings provide theoretical and experimental support for the development of new flavone-based candidates for cervical cancer therapy.

This paper reports the synthesis of benzo[d]oxazolo[2,3-a]isoquinoliniums as a novel ring system, its molecular structure, and spectroscopic properties. The target compounds were synthesized using an Ag-mediated intramolecular nucleophilic cyclization of 2-(2-arylethynylphenyl)benzoxazoles. The X-ray diffraction results revealed that the tetracyclic cation compound contained mostly planar parent skeletons and interacted via π–π stacking with neighboring molecules. Furthermore, in methanol solution, the benzoxazoloisoquinolines exhibited fluorescence with a large Stokes shift in the 350–550 nm region.

The application of the Huisgen cycloaddition reaction between acyl phosphonates (dipolarophile) and highly reactive intermediate nitrile imines (NI) as a 1,3-dipole in situ generated by the conversion of hydrazonyl chlorides in the presence of a base is reported to synthesize the phosphonate-containing 1,3,4-oxadiazole compounds in 53%–89% yields. Oxadiazole compounds stand out as significant target molecules in drug design and development due to their potential biological activities. Having a phosphonate group in the structure of the 1,3,4-oxadiazole may enhance biological activity be enhanced. We have synthesized 10 new phosphonate-containing oxadiazole compounds that are fully characterized by using spectroscopic analysis. Density Functional Theory (DFT) calculations were carried out to compare the energies of the frontier orbitals of the acyl phosphonates (dipolarophile) and NI (1,3 dipole) to determine the nature of the interaction between the dipolarophile and the 1,3-dipole. The relevant Huisgen cycloaddition reaction proceeds via a normal-electron demand (NED) pathway.

In this study, we have designed and synthesized a series of novel 1,2,3,4-tetrahydroisoquinoline-isatin derivatives, which were characterized by ¹H NMR and ¹³C NMR and HRMS. These compounds were evaluated for their potential anticancer activities against three human cancer cell lines (A549, HepG2 and Hela) by MTT assay in vitro. According to the IC₅₀ values, most of the compounds showed high activities against A549 (IC₅₀ = 6.47–25.08 μM), HepG2 (IC₅₀ = 2.55–46.85 μM), and Hela (IC₅₀ = 0.0067–87.35 μM), respectively. In particular, compound 6g showed the highest activity and selectivity against Hela (IC₅₀ = 6.7 nM). The results of cell migration and colony formation assays suggested that compounds (6k, 6m, and 6n) can effectively suppress the migration and growth of A549, HepG2, and Hela cells. In addition, the strong interaction and excellent binding affinity between potential active compounds (6g, 6p and 6q) and the active sites of CDK-5 were confirmed by molecular docking studies. Therefore, 1,2,3,4-tetrahydroisoquinoline-isatin hybrids might be considered as promising lead scaffolds for CDK-5 inhibitors.

Herein, we report the successful synthesis of some novel 3-thioether-linked 1,2,4-triazole-furoate hybrids (2a–f and 3a–c) in excellent yields. Structural characterization of all the compounds was accomplished via NMR spectroscopy and X-ray crystallography for 2f (CCDC No. 2457105), confirming the formation of the target hybrids. Biological evaluation revealed notably diverse bioactivities: antiproliferative activities of all the compounds against PANC-1 and three compounds against Huh7 cells were evaluated via CCK-8 assay, with 3c showing obvious efficacy (IC₅₀ = 20.37 μg/mL against Huh7). Significantly, 2a displayed potent growth-promoting effects on the Gram-negative bacterium Pseudomonas aeruginosa and the fungus Candida albicans, with remarkable promotion rates of 5525.00% and 500%, respectively. In contrast, it exhibited moderate inhibitory effects against Staphylococcus aureus (31.25%), Escherichia coli (55.56%), and Klebsiella pneumoniae (18.75%). 2b, 2d, 2f, and 3b showed remarkable growth-promoting effects on both wheat stalks and radicles at a concentration of 100 ppm, with their promotion rates reaching 96.3% and 123.9%, 113.5% and 137.9%, 126.1% and 177.7%, 99.4% and 107.6%, respectively, indicating their potential as wheat growth promoters.