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Background: Carbazole-based molecules containing thiosemicarbazide functional groups are recognized for their diverse biological activities, particularly in enhancing therapeutic anticancer effects through inhibiting crucial pathways. These derivatives also exhibit noteworthy antioxidant properties. Objectives: This study aims to synthesize, characterize, and evaluate the antioxidant and anticancer activities of 18 novel carbazole derivatives. Methods: The radical scavenging capabilities of the compounds were assessed using the 2,2-diphenyl-1-picrylhydrazyl assay. Antiproliferative activities were evaluated on MCF-7 cancer cell lines through viability assays. Additionally, the modulation of the PI3K/Akt/mTOR pathway, apoptosis/necrosis induction, and cell cycle analysis were conducted for the most promising anticancer agents. Results: nine compounds showed potent antioxidant activities with IC50 values lower than the positive control acarbose, with compounds 4 h and 4y exhibiting the highest potency (IC50 values of 0.73 and 0.38 µM, respectively). Furthermore, compounds 4o and 4r displayed significant anticancer effects, with IC50 values of 2.02 and 4.99 µM, respectively. Compound 4o, in particular, exhibited promising activity by targeting the PI3K/Akt/mTOR signaling pathway, inhibiting tumor survival, inducing apoptosis, and causing cell cycle arrest in MCF-7 cell lines. Furthermore, compound 4o was showed significant antimicrobial activities against S. aureus and E. coli, and antifungal effect against C. albicans. Its potential to overcome drug resistance through this pathway inhibition highlights its promise as an anticancer agent. Molecular docking simulations supported these findings, revealing favorable binding profiles and interactions within the active sites of the enzymes PI3K, AKT1, and mTOR. Moreover, assessing the druggability of the newly synthesized thiosemicarbazide derivatives demonstrated optimal physicochemical properties, further endorsing their potential as drug candidates. [ABSTRACT FROM AUTHOR]

In the 1980s, the identification of specific pharmacological antagonists played a crucial role in enhancing our comprehension of the physiological mechanisms associated with α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs). The primary objective of this investigation was to identify specific AMPA receptor antagonists, namely 2,3-benzodiazepines, that function as negative allosteric modulators (NAMs) at distinct locations apart from the glutamate recognition site. These compounds have exhibited a diverse array of anticonvulsant properties. In order to conduct a more comprehensive investigation, the study utilized whole-cell patch-clamp electrophysiology to analyze the inhibitory effect and selectivity of benzodiazepine derivatives that incorporate coumarin rings in relation to AMPA receptors. The study's main objective was to acquire knowledge about the relationship between the structure and activity of the compound and comprehend the potential effects of altering the side chains on negative allosteric modulation. The investigation provided crucial insights into the interaction between eight CD compounds and AMPA receptor subunits. Although all compounds demonstrated effective blockade, CD8 demonstrated the greatest potency and selectivity towards AMPA receptor subunits. The deactivation and desensitization rates were significantly influenced by CD8, CD6, and CD5, distinguishing them from the remaining five chemicals. The differences in binding and inhibition of AMPA receptor subunits can be attributed to structural discrepancies among the compounds. The carboxyl group of CD8, situated at the para position of the phenyl ring, substantially influenced the augmentation of AMPA receptor affinity. The findings of this study highlight the potential of pharmaceutical compounds that specifically target AMPA receptors to facilitate negative allosteric modulation. [ABSTRACT FROM AUTHOR]

Background: The carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities. Objectives: This study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities. Methods: The synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Results: A series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2–5 against HepG2, HeLa, and MCF7 cancer cell lines with IC50 values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 values in the range of 43.7–187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively. Conclusion: Most of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results. [ABSTRACT FROM AUTHOR]

The 2D hybrid compound bis(2-amino-4-methoxy-6-methylpyrimidinium) bis(μ2-chloro)-tetrachloro-di-copper(II), (C6H10N3O)2Cu2Cl6, is successfully synthesized by slow solvent evaporation at room temperature. Structural properties have been investigated through single-crystal X-ray diffraction and reveal that the structure contains a centrosymmetric hexachlorodicuprate group where each Cu atom is coordinated to four Cl atoms in a slightly distorted square planar geometry. There are short contacts between neighboring [Cu2Cl6]2− dimer units. The crystalline building stability is ensured by N–H⋯Cl and C–H⋯O hydrogen bonding as well as weak C–H···π intermolecular interactions. From the infrared spectroscopy analysis, the functional groups were identified. Simultaneously, the electrical properties and Hirshfeld surface analyses were also elucidated. Furthermore, the molecular docking study of 2D hybrid compound bis(2-amino-4-methoxy-6-methylpyrimidinium) bis(2-chloro)-tetrachloro-di-copper(II) ligand with an HSP90/PDB: 5LRZ was performed by Autodock Vina. Additionally, drug-likeness and ADME properties and evaluations of the newly synthesized molecule were performed in detail. FT-IR was used to explore the modes of vibration of the different functional groups present in the studied compound. [ABSTRACT FROM AUTHOR]

The 2D hybrid compound bis(2-amino-4-methoxy-6-methylpyrimidinium) bis(μ2-chloro)-tetrachloro-di-copper(II), (C6H10N3O)2Cu2Cl6, is successfully synthesized by slow solvent evaporation at room temperature. Structural properties have been investigated through single-crystal X-ray diffraction and reveal that the structure contains a centrosymmetric hexachlorodicuprate group where each Cu atom is coordinated to four Cl atoms in a slightly distorted square planar geometry. There are short contacts between neighboring [Cu2Cl6]2− dimer units. The crystalline building stability is ensured by N–H⋯Cl and C–H⋯O hydrogen bonding as well as weak C–H···π intermolecular interactions. From the infrared spectroscopy analysis, the functional groups were identified. Simultaneously, the electrical properties and Hirshfeld surface analyses were also elucidated. Furthermore, the molecular docking study of 2D hybrid compound bis(2-amino-4-methoxy-6-methylpyrimidinium) bis(2-chloro)-tetrachloro-di-copper(II) ligand with an HSP90/PDB: 5LRZ was performed by Autodock Vina. Additionally, drug-likeness and ADME properties and evaluations of the newly synthesized molecule were performed in detail. FT-IR was used to explore the modes of vibration of the different functional groups present in the studied compound. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents" published in BMC Chemistry. The correction addresses an affiliation error in the supplementary material and states that it has been replaced with the correct file. The original article has been corrected. The document also includes the names of the authors involved in the study. [Extracted from the article]