Search Results (146)

The terpeno-heterocyclic molecular hybrids are a new and promising class of modern organic and medicinal chemistry, because their molecules exhibit high and selective biological activity, natural origins, and good biocompatibility, and, usually, they are less toxic. The reported norlabdane-heterocyclic hybrids were synthesized by classical and new, original, and environmentally friendly methods, which include coupling reactions of norlabdane derivatives (such as carboxylic acids, acyl chlorides, or bromides) with individual heterocyclic compounds, as well as heterocyclization reactions of certain norlabdane intermediates like hydrazides, thiosemicarbazones, or hydrazinecarbothioamides. The aforementioned norlabdanes were derived from (+)-sclareolide 2, which is readily obtained from (−)-sclareol 1, a labdane-type diterpenoid extracted from the waste biomass of Clary sage (Salvia sclarea L.) that remains after essential oil extraction. All synthesized compounds were tested against various fungal strains and bacterial species, with many exhibiting significant antifungal and antibacterial activity. These findings support the potential application of the synthesized compounds in the treatment of diseases caused by fungi and bacteria. Additionally, the use of plant-based waste materials as starting resources highlights the economic and ecological value of this approach. This review summarizes experimental data on the synthesis and biological activity of norlabdane: diazine, 1,2,4-triazole and carbazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,3-thiazole, 1,3-benzothiazole and 1,3-benzimidazole hybrids performed by our research group covering the period from 2013 to the present. Full article

Macrocyclic arenes are rich-electron macrocycles bridged by methylene or methyl groups from aromatic rings substituted by hydroxyl or alkoxy groups. It has attracted great interest in host–guest chemistry and supramolecular self-assembly due to its clear cavity, adjustable structure and multifunctional binding ability. In particular, nitrogen-containing macrocyclic arenes including (hetero) aromatic moieties—constructed from building blocks such as pyrrole, carbazole, phenothiazine, and imidazole—have undergone rapid development, yielding a new generation of functional macrocycles, including calix[4]carbazoles, Tröger’s base-derived macrocycles, and phenothiazine-based architectures. These nitrogen-functionalized macrocycles feature rich chemical derivatization potential, unique structural and host–guest characteristics, and exceptional photophysical properties. They show great promise in molecular recognition, selective adsorption and separation, and the development of advanced functional materials. This review summarizes recent advances in the design, synthesis, and application of nitrogen-containing macrocyclic arenes, with a particular focus on structure–property relationships and emerging functions. Full article

Cancer is one of the leading causes of human mortality worldwide, and aberrant expression of the c-myb oncogene is closely associated with the development of numerous malignancies. The c-myb promoter region contains G-rich and C-rich sequences capable of forming G-quadruplex (G4) and i-motif (IM or C-quadruplex) structures, respectively. These secondary structures function as “molecular switches” for gene transcriptional regulation and represent promising targets for novel anti-tumor therapeutics. Through extensive screening, we identified carbazole derivative G51 as a unique dual-targeting ligand that simultaneously destabilized the i-motif and stabilized the G-quadruplex, consequently suppressing c-myb expression efficiently. In comparison, the single-targeting ligand G50, which could specifically bind to and unfold the G-quadruplex only, exhibited significantly weaker anti-tumor activity than G51. Notably, G51 showed potent anti-tumor efficacy in a human colorectal cancer xenograft model without significant toxicity to vital organs. G51, as a dual-targeting ligand, had specific binding to c-myb promoter quadruplexes, with destabilization of the i-motif and concurrent stabilization of the G-quadruplex. This opposing effect could provide a good opportunity for specific gene regulation, with great potential for further development of a precise therapeutic agent. This study provides a novel example for a practical therapeutic approach through coordinated gene quadruplex modulations, which sets up a good foundation for developing high-efficacy anti-tumor drugs without significant side effects. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article

Two innovative dimeric derivatives of indolo[3,2,1-jk]carbazole (ICz), named 7,7′-biindolo[3,2,1-jk]carbazole (ICzDO) and 4,4′-biindolo[3,2,1-jk]carbazole (ICzDM), have been developed. Both dimers consist of two ICz units coupled through distinct ortho and meta positions. In the solution state, ICzDO and ICzDM exhibited photoluminescence (PL) maxima at 379 nm and 391 nm, demonstrating emission in the deep-blue region. These compounds show exceptionally narrow emission spectra, characterized by full width at half maximum (FWHM) of 28 nm for ICzDO and 26 nm for ICzDM. In the film state, ICzDM exhibited a photoluminescence (PL) maximum at 428 nm, whereas ICzDO showed a red-shifted emission at 507 nm with a broad full width at half maximum (FWHM) of 87 nm, indicating significant red-shifted excimer emission characteristics. This is attributed to its aggregation-enhanced excimer emission (AEEE) characteristics. When used as host materials for red phosphorescent OLEDs, both compounds enabled efficient energy transfer. Devices using ICzDM as the host attained highly efficient external quantum efficiency (EQE) values of 13.5%, coupled with remarkable color purity represented by Commission Internationale de l’Éclairage (CIE) coordinates of (0.685, 0.314). These findings emphasize how strategic variations in linking positions of identical chromophores can markedly enhance OLED device performance, paving the way for innovative material designs in next-generation organic semiconductor technologies. Full article

Background: Cancer remains a leading cause of morbidity and mortality worldwide. According to the World Health Organization (WHO), lung cancer is the most prevalent type of cancer among both men and women. Despite the various pharmacological and biological treatments available for lung cancer, their effectiveness has often fallen short, and the side effects can be severe. Therefore, there is an ongoing need to identify and develop novel compounds with enhanced anti-tumor efficacy and improved safety profiles. Research has shown that fluoroquinolone derivatives exhibit a broad cytotoxic spectrum comparable to other drugs used in clinical chemotherapy. Objective: The aim of this work was to synthesize and evaluate the cytotoxic, anti-proliferative, and anti-tumor effects of FQB-1, a novel fluoroquinolone derivative. Results: In silico molecular docking analysis demonstrated a strong interaction between FQB-1 and human topoisomerase, with a binding affinity score of –9.8 kcal/mol. In vitro cytotoxicity and anti-proliferative assays were conducted using the Lewis Lung Carcinoma (LLC) cell line. FQB-1 was tested at concentrations of 2.5, 5.0, 25.0, 50.0, 100.0, and 150.0 µg/mL. Significant cytotoxic and anti-proliferative effects were observed at concentrations of 50–150 µg/mL after 24 h of treatment. To evaluate FQB-1′s efficacy in vivo, a syngeneic tumor model was established in C57BL/6 mice. Treatment with FQB-1 (100 mg/kg) resulted in a marked reduction in tumor volume compared to the untreated control group. Histopathological analysis of tumor tissues from treated animals revealed a decrease in mitotic index and an increase in necrotic regions, indicating compromised tumor viability. Conclusions: FQB-1 exhibits cytotoxic and anti-proliferative effects and can reduce tumor growth while compromising tumor viability. Full article

Here, we present two series of new electroactive compounds containing electron donors (carbazolyl) and electron acceptor (pyridinyl) fragments as potential host materials. The objective compounds 9-(2-ethylhexyl)-3,6-di [3-(methoxypyridin-3-yl)carbazol-9-yl]carbazoles RB71 and RB74 were synthesized by an Ullmann coupling reaction between the intermediate derivatives: 9-(2-ethylhexyl)-3,6-diiodocarbazole and corresponding 3-(methoxypyridin-3-yl)-9H-carbazole. Other target derivatives, 9-alkyl-3-[N-(9-alkylcarbazol-3-yl)-N-(4-methylpyridin-2-yl)amino]carbazoles RB70 and RB75, were also prepared, according to the Ullmann reaction method, from 2-amino-4-methylpyridine and the corresponding 3-iodo-9-alkylcarbazole. Thermogravimetric analysis confirmed that the new derivatives are highly thermally stable compounds, with 5% weight loss in the temperature range of 349 °C to 488 °C. According to differential scanning calorimetry results, some amorphous materials exhibit very high glass transition temperatures exceeding 150 °C in some cases, which is a significant advantage for compounds with potential applications in organic light-emitting devices. The electroluminescent properties of devices utilizing the new hosts RB71 or RB70 with 5.0, 10.0, 15.0, and 20.0 wt.% concentrations of the dopant tris(2-phenylpyridine)iridium(III), Ir(ppy)₃, were demonstrated. All the PhOLEDs emitted light at approximately 515 nm with CIE coordinates of (0.30, 0.61) due to Ir(ppy)₃ emissions. The most efficient device with RB71 host demonstrated a maximum power efficacy of 8.0 lm/W, maximum current efficiency of 12.7 cd/A, and maximal external quantum efficiency of 5.4% with a relatively low turn-on voltage of 4.3 eV, as well as luminance exceeding 4000 cd/m². Additionally, 15 wt.% Ir(ppy)₃ emitter-based PhOLED with RB70 host outperformed the other devices by displaying a maximum power efficacy of 9.6 lm/W, maximum current efficiency of 16.0 cd/A, and maximal external quantum efficiency of 6.7% with a relatively low turn-on voltage of 3.7 eV, as well as luminance reaching 11,200 cd/m². Some devices seem to exhibit higher efficiencies than those previously reported for OLEDs that utilize a 4,4′-bis(9-carbazolyl)-2,2′-biphenyl (CBP) host. Full article

The second-generation phosphorescent organic light-emitting diodes are formed using phosphorescent emitters, which can theoretically achieve 100% internal quantum efficiency. However, these emitting materials usually suffer from triplet–triplet annihilation (TTA) and/or concentration-quenching effects. To address the disadvantages, host–guest systems are used in the emitting layer, where the guest is dispersed into a host matrix. Carbazole is one of the most commonly used electron-donating fragments, which is widely applied as a building block for the synthesis of the mentioned host materials. In this review article, we describe the synthesis, thermal, electrochemical, and optoelectronic properties of the hosts with carbazolyl units as well as application of the matrixes in the phosphorescent devices. This review is written from the perspective of structural chemistry and the host materials are divided in several groups as 9-arylcarbazoles, twin derivatives containing two carbazolyl fragments, 3(2)-aryl(arylamino)-substituted, and 3,6(2,7)-diaryl(diarylamino)-substituted carbazoles. Full article

Background: Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. Objectives/Methods: In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. Results: This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. Conclusions: Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications. Full article

Simple substitutions on the donor or acceptor units in radicals is an effective method to improve luminescent properties. However, the luminescence efficiency of radicals has not yet reached satisfactory levels through simple molecular structure modification. In this study, two [4-(N-Carbazolyl)-2,6-dichlorophenyl] bis(2,4,6-trichlorophenyl)methyl (Cz-TTM) radical derivatives (Mes₂Cz-TTM, Mes₂Cz-Mes₂TTM) were synthesized and characterized by modifying the carbazole (donor) and tris-2,4,6-trichlorophenylmethyl radical (acceptor) units with 2,4,6-trimethylphenyl groups. The different substitutions showed varying influences on photoluminescence quantum efficiency (PLQE) compared to the Cz-TTM parent radical. The donor-only substitution suppressed the PLQE (39%) in Mes₂Cz-TTM. In contrast, Mes₂Cz-Mes₂TTM exhibited a significantly higher PLQE of 92.6%, compared to the 68% PLQE of the Cz-TTM parent radical in toluene. Additionally, thermostability and photostability were improved with both donor and acceptor substitutions. The photophysical properties, molecular orbitals, and electrochemical behaviors were also systematically explored. This strategy provides a feasible approach to achieve high luminescence efficiency in radicals through simple substitutions on donor and acceptor units. Full article

In the last decade, the aryl hydrocarbon receptor (AHR) has emerged as a critical peacekeeper for the maintenance of healthy skin. The evolutionary conservation of AHR implied physiological functions for this receptor, beyond the detoxification of man-made compounds, a notion further supported by the existence of physiological AHR ligands, notably derivates of tryptophan by the host and host microbiome. The UV light-derived ligand, 6-formylindolo[3,2-b]carbazole (FICZ), anticipated a role for AHR in skin, a UV light-exposed organ, where physiological AHR activation promotes a healthy skin barrier and constrains inflammation. The clinical development of tapinarof, the first topical AHR modulating drug for inflammatory skin disease, approved by the FDA for mild-to-moderate psoriasis and poised for approval in atopic dermatitis, supports the therapeutic targeting of the AHR pathway to harness its beneficial effect in skin inflammation. Here, we describe how a tightly controlled, physiological activation of the AHR pathway maintains skin homeostasis, and discuss how the pathway is dysregulated in psoriasis and atopic dermatitis, identifying areas offering opportunities for alternative therapeutic approaches, for further investigation. Full article

The Aryl-hydrocarbon Receptor (AhR) is implicated in the regulation of several genes, including those encoding CYP1A1. Although it is an orphan receptor, the amount of data about its relationship with skin homeostasis and nosology is constantly increasing. Interestingly, 6-formylindolo[3,2-b]carbazole (6-FICZ), one of the most active AhR inducers and amongst the proposed receptor’s endogenous ligands, has been detected in Malassezia furfur isolates from lesional skin, as well as in skin scales from patients with seborrhoeic dermatitis. Aiming to study the structure–activity relationships of the indolo[3,2-b]carbazole (ICZ) scaffold and to clarify if the formyl group of 6-FICZ has any specific role in AhR induction, a series of analogues of ICZ (substituted at position 6 with methyl, formyl and hydroxymethyl groups) were synthesized and evaluated for their activity on AhR in cell lines of four different species. A new simple method for the synthesis of 6-FICZ was developed. 6-Methylindolo[3,2-b]carbazole (6-MICZ) showed higher activity than 6-FICZ in human, rat and guinea pig cell lines, and all synthesized derivatives showed comparable activity in the mouse cell line. Therefore, the formyl group does not seem to play a significantly specific role in the affinity for AhR, and 6-FICZ seems less likely to be an endogenous ligand. Full article

Fusarium fungi are widespread pathogens of food crops, primarily associated with the formation of mycotoxins. Therefore, effective mitigation strategies for these toxicogenic microorganisms are required. In this study, the potential of pulsed electric field (PEF) as an advanced technology of increasing use in the food processing industry was investigated to minimize the viability of Fusarium pathogens and to characterize the PEF-induced changes at the metabolomic level. Spores of four Fusarium species (Fusarium culmorum, Fusarium graminearum, Fusarium poae, and Fusarium sporotrichioides) were treated with PEF and cultured on potato dextrose agar (PDA) plates. The viability of the Fusarium species was assessed by counting the colony-forming units, and changes in the mycotoxin content and metabolomic fingerprints were evaluated by using UHPLC-HRMS/MS instrumental analysis. For metabolomic data processing and compound identification, the MS-DIAL (v. 4.80)–MS-CleanR–MS-Finder (v. 3.52) software platform was used. As we found out, both fungal viability and the ability to produce mycotoxins significantly decreased after the PEF treatment for all of the species tested. The metabolomes of the treated and untreated fungi showed statistically significant differences, and PEF-associated biomarkers from the classes oxidized fatty acid derivatives, cyclic hexapeptides, macrolides, pyranocoumarins, carbazoles, and guanidines were identified. Full article

Carbazoles and their derivatives are ubiquitous in organic electronics since these compounds combine relatively low cost, chemical and thermal stability, and good hole transport properties, along with a tunable electronic structure. Thus, the application of carbazole molecules in the development of optoelectronic and photovoltaic devices, such as OLEDs and solar cells, has been explored with different patterns of functionalization (N-substitution, di- and polyfunctionalization) in the quest for increased efficiencies. In this review, we provide a brief overview of the basic aspects related to solar cells and OLEDs with a focus on the applications involving these versatile and promising building blocks. Full article

Phenoxazine, as an organic-small-molecule chromophore, has attracted much attention for its potential electrochromic applications recently. To develop appealing materials, phenoxazine chromophores were introduced at the N-position of carbazole–thiophene pigment, yielding two novel monomers (DTCP and DDCP), whose chemical structures were characterized by NMR, HRMS and FTIR. The results of the optical property study indicate that little influence could be observed in the presence of the phenoxazine chromophore. Corresponding polymer films on the surface of an ITO/glass electrode were obtained through electropolymerization. The electrochemical features displayed were various due to the introduction of the phenoxazine group. The spectroelectrochemical results demonstrate that the color of the polymer films could be changed. Compared with the PDDC films, the PDDCP films exhibited three different colors (tangerine, green and purple colors) in different redox states, which could be attributed to the synergistic effect between the carbazole–thiophene conjugate chain and the phenoxazine group. Moreover, fast switching time could be seen due to the presence of the phenoxazine chromophore. This study could provide a reference for obtaining high-performance electrochromic materials. Full article