More Than Carbazole Derivative Activates Room Temperature Ultralong Organic Phosphorescence of Benzoindole Derivative

Herein, we report four carbazole/1H-benzo[f]indole (Cz/Bd) derivatives with increasing Bd substitution (Bd number=0~3), which give a general mechanism for Bd-based ultralong organic phosphorescence. To physically isolate Cz and Bd, we synthesized Cz and Bd in the lab, separately. According to experimental results, we draw several important points. The first important point is that Bd and its derivatives commonly possess two groups of intrinsic phosphorescence bands, of which short-lifetime band at ~450 nm is assigned to the molecular phosphorescence of their neutral molecules and of which typical ultralong phosphorescence bands at 560 nm, 610 nm and 660 nm are assigned to their radical cations. Amazingly, PMMA films (1wt.%) of CNCzBdBr and CN2BdBr both demonstrate photo-activated room-temperature ultralong organic phosphorescence while this doesn’t happen to Bd and CN3Bd. The second important point is that activation of ultralong phosphorescence from Bd derivatives involves three factors: well dispersion with limited amount in matrix, generation of Bd derivatives’ radical cations and stabilizing radical cations mediated by matrix. Cz derivative can function as a matrix to activate (room temperature) ultralong organic phosphorescence of Bd derivative but its activation function can be replaced by other methods such as photo-activation. The third important point is that the photo-activated ultralong organic phosphorescence is closely related to molecular structure of Bd derivative and stability of its radical cation. The fourth important point is that for double-carbazole system with trace isomer its room temperature ultralong organic phosphorescence originates at least from synergistic effect of monosubstituted product and disubstituted product of Bd. Furthermore, it is discovered that several other matrixes can also activate room-temperature ultralong organic phosphorescence of Bd derivatives, further verifying the second important point. To our best knowledge, this study is a big breakthrough in ultralong organic phosphorescence and will probably open a new era for its development.

Evaluation of the Antimicrobial Potential and Toxicity of a Newly Synthesised 4-(4-(Benzylamino)butoxy)-9H-carbazole

One of the greatest threats to human and animal health is posed by infections caused by drug-resistant bacterial strains. Therefore, newly synthesised substances are tested for their antimicrobial activity. Carbazole derivatives seem to be promising antibacterial agents. This study aimed at investigating the toxicity and activity of newly synthesised, functionalised carbazole derivative 2 (4-(4-(benzylamino)butoxy)-9H-carbazole) against various microorganisms. Its antimicrobial potential against Gram-positive and Gram-negative bacteria, yeast, and filamentous fungi was examined according to CLSI (Clinical and Laboratory Standards Institute) standards. The tested compound was found to efficiently inhibit the growth of Gram-positive strains. The addition of carbazole derivative 2 at the concentration of 30 µg/mL caused inhibition of bacterial growth by over 95%. Moreover, about 50 and 45% limitation of Pseudomonas aeruginosa and Aspergillus flavus growth was observed in the samples incubated with the addition of 20 and 60 µg/mL of the compound, respectively. Its addition to the microbial cultures caused an increase in the permeability of the cellular membrane. Slight haemolysis of red blood cells was observed after 24-h treatment with carbazole derivative 2. On the other hand, human fibroblasts were found to be more sensitive to its effects. The activity of the tested compound indicates a possibility of its further modification in order to obtain effective drugs, especially against drug-resistant staphylococci.

Carbazole and Simplified Derivatives: Novel Tools toward β-Adrenergic Receptors Targeting

β-Adrenergic receptors (β-ARs) are G protein-coupled receptors involved in important physiological and pathological processes related to blood pressure and cardiac activity. The inhibition of cardiac β1-ARs could be beneficial in myocardial hypertrophy, ischemia and failure. Several carbazole-based compounds have been described as promising β-blockers. Herein, we investigate the capability of a carbazole derivative and three simplified indole analogs to interact with the active binding site of β1-AR by molecular docking studies. In the light of the obtained results, our compounds were tested by biological assays in H9c2 cardiomyocytes exposed to isoproterenol (ISO) to confirm their potential as β1-blockers agents, and two of them (8 and 10) showed interesting and promising properties. In particular, these compounds were effective against ISO-dependent in vitro cardiac hypertrophy, even at concentrations lower than the known β-AR antagonist propranolol. Overall, the data suggest that the indole derivatives 8 and 10 could act as potent β1-blockers and, active at low doses, could elicit limited side effects.

A carbazole compound, 9-ethyl-9H-carbazole-3-carbaldehyde, plays an antitumor function through reactivation of the p53 pathway in human melanoma cells

Abstractp53, the major tumor suppressor, is frequently mutated in many cancers, and up to 84% of human melanomas harbor wild-type p53, which is considered to be an ideal target for melanoma therapy. Here, we evaluated the antitumor activity of a carbazole derivative, 9-ethyl-9H-carbazole-3-carbaldehyde (ECCA), on melanoma cells. ECCA had a selectively strong inhibitory activity against the growth of BRAF-mutated and BRAF-wild-type melanoma cells but had little effect on normal human primary melanocytes. ECCA inhibited melanoma cell growth by increasing cell apoptosis, which was associated with the upregulation of caspase activities and was significantly abrogated by the addition of a caspase inhibitor. In vivo assays confirmed that ECCA suppressed melanoma growth by enhancing cell apoptosis and reducing cell proliferation, and importantly ECCA did not have any evident toxic effects on normal tissues. RNA-Seq analysis identified several pathways related to cell apoptosis that were affected by ECCA, notably, activation of the p53 signaling pathway. Biochemical assays demonstrated that ECCA enhanced the phosphorylation of p53 at Ser15 in melanoma cells harboring wild-type p53, and importantly, the knockdown or deletion of p53 in those cells counteracted the ECCA-induced apoptosis, as well as senescence. Further investigations revealed that ECCA enhanced the phosphorylation of p38-MAPK and c-Jun N-terminal kinase (JNK), and treatment with either a p38-MAPK or a JNK inhibitor rescued the cell growth inhibition elicited by ECCA, which depended on the expression of the p53 gene. Finally, the combination of ECCA with a BRAF inhibitor significantly enhanced the growth inhibition of melanoma cells. In summary, our study demonstrates that the carbazole derivative, ECCA, induces melanoma cell apoptosis and senescence through the activation of p53 to significantly and selectively suppress the growth of melanoma cells without affecting normal human melanocytes, suggesting its potential to develop a new drug for melanoma therapy.