Carbazole Hybrid Research Articles

A Review of In Vitro Antimicrobial Activities of Carbazole and its Derivative From 2014 to 2022

Abstract: A large number of antibiotics are easily accessible for the treatment of various micro-bial infections. However, antibiotic resistance has become a major concern to public health across the globe. Carbazole derivatives are present in carbazomycins, an unprecedented class of antibiotics showing potential antibacterial activities. As reported in the literature, carbazole de-rivatives also possess significant antimicrobial activities against bacterial resistance, such as Methicillin Resistant Staphylococcus aureus (MRSA). The antimicrobial profile of carbazole derivatives has been achieved through various bacterial pathways. Carbazole hybrids based on the multi-target direct ligand (MTDL) approach were also extensively studied as they exhibited significant antibacterial activities. This article reviews antimicrobial potential, docking analysis, and structure-activity relationship (SAR) studies of carbazole and its derivatives against tested bacterial strains from 2014 to 2022. This review can also be helpful for investigators in the de-sign and development of new molecules based on carbazole structure against various resistant bacterial infections.

Recent advancement of carbazole hybrid: a privileged scaffold in new drug discovery

Recent advancement of carbazole hybrid: a privileged scaffold in new drug discovery

Design and Synthesis of Aminoacetylenic Indole and Carbazole Hybrid Compounds

AbstractA novel series of aminoacetylenic indole and carbazole hybrid compounds had been prepared via a three‐component reaction system in which a mannich type reaction was used in the coupling of propargylic indole or carbazole with cyclic amines and formaldehyde in the presence of Cu(I) catalyst. A side product of the self‐coupling reaction of propargylic indole was also separated and characterized by physicochemical techniques. NMR, single crystal x‐ray, High‐resolution mass spectra (HRMS) are used in the characterization of the synthesized compounds and intermediates

Synthesis and Biological Evaluation of Novel Carbazole Hybrids as Promising Antimicrobial Agents.

Two series of carbazole analogs of 8-methoxy-N-substituted-9H-carbazole-3-carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 μg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 μg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 μg/mL) and S. aureus (MIC: 1.56 μg/mL), respectively.

Design, Synthesis, and Evaluation of Isoxazole-Thiadiazole Linked Carbazole Hybrids as Anticancer Agents

A series of isoxazole-thiadiazole linked carbazole derivatives 12a–12j are synthesized and their chemical structures confirmed by 1H and 13C NMR and mass spectra. The products are tested for their anticancer activity against human cancer cell lines: MCF-7 (breast), A549 (lung), DU-145 (prostate), and MDA MB-231 (breast) by using MTT assay and etoposide as a reference drug. The accumulated data indicate that most of the compounds demonstrate anticancer activity higher than etoposide.

Highly efficient TADF OLEDs with low efficiency roll-off based on novel acridine–carbazole hybrid donor-substituted pyrimidine derivatives

Dimethyl acridine (Ac) and carbazole (Cz) donors are fused to produce acridine–carbazole hybrid donors 12AcCz (8,8-dimethyl-5-phenyl-8,13-dihydro-5H-indolo[2,3-c]acridine) and 23AcCz (13,13-dimethyl-7-phenyl-7,13-dihydro-5H-indolo[3,2-b]acridine).

Integrating TADF luminogens with AIE characteristics using a novel acridine–carbazole hybrid as donor for high-performance and low efficiency roll-off OLEDs

A novel acridine–carbazole hybrid donor (34AcCz: 13,13-dimethyl-8-phenyl-8,13-dihydro-5H-indolo[3,2-a]acridine) was formed from two sophisticated donors of dimethyl acridine (DMAc) and carbazole (Cz).

Cyanopyrimidine-Carbazole Hybrid Host Materials for High-Efficiency and Low-Efficiency Roll-Off TADF OLEDs.

Two isomeric host materials (Sy and Asy) comprising carbazole (donor) and CN-substituted pyrimidine (acceptor) were synthesized, characterized, and utilized as host materials for green and blue thermally activated delayed fluorescence (TADF) organic light emitting diodes (OLEDs). Both molecules have high triplet energy and small energy difference between singlet and triplet states, leading to feasible TADF. The different linking topologies of carbazole and CN groups on the pyrimidine core provide distinct photophysical properties and molecular packing manners, which further influence the efficiency as they served as hosts in TADF OLEDs. As compared to Asy-based cases, the Sy-hosted TADF OLED device gave higher maximum external quantum efficiencies (EQE) of 24.0% (vs 22.5%) for green (4CzIPN as a dopant) and 20.4% (vs 15.0%) for blue (2CzTPN as a dopant) and low efficiency roll-off. The high horizontal dipole ratio (Θ ≈ 88%) for both emitters dispersed in Sy and Asy hosts accounts for the high device efficiency. A clear molecular structure-physical property-device performance relationship has been established to highlight the importance of symmetrical structure in TADF host material design.

Synthesis and larvicidal activities of compounds based on coumarin and dibenzothiophene/carbazole

Based on a rationally conceived pharmacophore model to build a dual-target mosquito larvicide, a family of coumarin-dibenzothiophene or -carbazole hybrids with various substituents on phenyl were synthesized in moderate yields. Larvicidal activity of hybrid molecules were evaluated against fourth instar larvae of Aedes aegypti. Most of the synthesized hybrids displayed moderate to high activity and the activities of coumarin-linked carbazole hybrids were better than those of dibenzothiophene hybrids. The structure–activity relationships revealed that coumarin, dibenzothiophene and carbazole were the key pharmacophore and carbazole derivatives consisting of an electron-withdrawing group in the coumarin–carbazole hybrid molecular structure possess better activity than their corresponding parent compound.

Bipolar Host Material for Phosphorescent OLEDs Based on 2,7‐Diazacarbazole as a New Electron‐transporting Unit

The novel electron‐transporting moiety of 2,7‐diazacarbazole was used to construct a bipolar host molecule for phosphorescent organic light‐emitting diodes (PHOLEDs). This moiety was incorporated with typical hole‐transporting carbazole moieties to synthesize a 2,7‐diazacarbazole/carbazole hybrid called 9‐(3,5‐bis(carbazol‐9‐yl)phenyl)–2,7‐diazacarbazole. The hybrid exhibits a high triplet energy above 2.88 eV and very high glass transition temperature of Tg = 148°C. It shows good thermal stability owing to the rigid nature of its symmetrical bipolar structure. The 2,7‐diazacarbazole‐based host material turns on at 3.6 and 3.7 V and approaches external quantum efficiencies above 16.0 and 22.6% in blue and green PHOLEDs, respectively. These results demonstrate that 2,7‐diazacarbazole should be an excellent electron‐transporting unit for bipolar phosphorescent hosts.

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents.

Ferulic acid–carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents

In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid–carbazole hybrid compounds were designed and synthesized. Ellman’s assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.

Improved host material for electrophosphorescence by positional engineering of spirobifluorene–carbazole hybrids

Two novel materials, SF2BCz and SF3BCz, which combine spirobifluorene (SF) and carbazole units by meta- and para-bonding, have been designed and synthesized by a straightforward process as hosts in phosphorescent organic light-emitting diodes (PhOLEDs), and their thermal and electronic absorption and photoluminescent properties investigated. The meta-linkage of SF enables SF3BCz to possess high triplet and energy levels and good thermal stability. Blue PhOLEDs featuring SF3BCz as a host give high performance and low roll-off, with an efficiency of 41.4 cd A−1 (39.8 lm W−1) at 100 cd m−2 and 39.7 cd A−1 (29.8 lm W−1) at 1000 cd m−2. In addition, SF3BCz has been adopted as a universal host for white PhOLEDs, with a maximum external quantum efficiency of 21.3% for two-color and 19.8% for three-color-based white devices. By adopting tandem technology, a four-color-based white PhOLED was also successfully constructed, achieving 40% external quantum efficiency and a stable color spectrum.

Synthesis, biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

New tacrine–carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.03 μM and exhibited good inhibition selectivity against AChE over butyrylcholinesterase (BuChE). Molecular modeling studies revealed that these tacrine–carbazole hybrids interacted simultaneously with the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The derivatives containing methoxy group showed potent ABTS radical scavenging activity. Considering their neuroprotection, our results indicate that these derivatives can reduce neuronal death induced by oxidative stress and β-amyloid (Aβ). Moreover, S1, the highest potency for both radical scavenging and AChE inhibitory activity, exhibited an ability to improve both short-term and long-term memory deficit in mice induced by scopolamine. Overall, tacrine–carbazole derivatives can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy.

A new multifunctional fluorenyl carbazole hybrid for high performance deep blue fluorescence, orange phosphorescent host and fluorescence/phosphorescence white OLEDs

A new multifunctional host material, 3,3′-(2,7-di(quinolin-8-yl)-9H-fluorene-9,9-diyl)bis(9-phenyl-9H-carbazole) has been designed, synthesized and used in high performance OLEDs. This tetrasubstituted fluorene was found to have good morphological and thermal stability with a high glass transition temperature of 192 °C and a decomposition temperature of 480 °C. A non-doped tri-layer blue fluorescent device based on this tetrasubstituted fluorene shows a deep blue emission with a Commission Internationale de L’Eclairage coordinates of (0.16, 0.10) and a maximum power efficiency of 1.1 lm/W. An orange phosphorescent device using this tetrasubstituted fluorene as a host in conjunction with an iridium complex as dopant exhibits a maximum power efficiency of 21.0 lm/W, which is much higher than that of a biscarbazolylbiphenyl-based control device (11.5 lm/W) with the same device structure. Furthermore, by using the tetrasubstituted fluorene as a blue florescent emitter and a host for phosphorescent dopant, a white emitting OLED with a maximum power efficiency of 22.5 lm/W and CIE coordinates of (0.38, 0.33) were obtained. These results show that this tetrasubstituted fluorene is a versatile multifunctional material for OLED applications.

Controllably tunable phenanthroimidazole–carbazole hybrid bipolar host materials for efficient green electrophosphorescent devices

A series of phenanthroimidazole–carbazole (1 : 2) hybrids as bipolar host materials have been designed and synthesized through facile typical Ullmann reactions. These compounds with rigid configurations exhibit excellent thermal and morphological stabilities with high glass transition temperatures (Tg) (143–282 °C). Their photoelectronic properties, energy levels, charge transport mobility, and film morphologies can be controllably tuned through judicious engineering of the linkage modes between the two carbazole groups and the 2,5-diphenyl-1,3,4-phenanthroimidazole (para and meta). The promising physical properties of these new compounds make them suitable for use as hosts doped with Ir-based phosphor for realizing highly efficient phosphorescent organic light emitting diodes (PhOLEDs). A green device hosted by compound PhBIDmpCP shows a maximum current efficiency of 74.3 cd A−1 and a maximum power efficiency of 74.4 lm W−1 (corresponding EQEmax = 20.2%).

New indole–carbazole hybrids as glass-forming high-triplet-energy materials

New indole–carbazole hybrids are reported as glass-forming high-triplet-energy materials. They were synthesized by the tandem addition–elimination–(Michael) addition reaction of 9-ethyl-9 H-carbazole-3-carbaldehyde with 1 H-indole or 2-phenyl-1 H-indole followed by alkylation with the different agents. The synthesized compounds exhibit moderate thermal stabilities with 5% weight loss temperatures ranging from 281 to 308 °C. Their glass transition temperatures are in the range of 89–143 °C. Most of the new indole–carbazole hybrids in dilute solutions exhibit high triplet energies (2.97–2.99 eV).