Spin-coated and vacuum-processed hole-extracting self-assembled multilayers with H-aggregation for high-performance inverted perovskite solar cells.

We report a highly crystalline self-assembled multilayer (SAMUL) that is fundamentally different from the conventional monolayer or disordered bilayer used for hole-extraction in inverted perovskite solar cells (PSCs). The SAMUL can be easily formed on ITO substrate to form better surface coverage for enhancing the performance and stability of PSCs. A detailed structure-property-performance relationship of molecules used for SAMUL is established through a systematic study of their crystallinity, molecular packing, and hole-transporting properties. These SAMULs are rationally optimized by varying their molecular structures and deposition through thermal evaporation or spin-coating for fabricating PSCs. The CbzNaphPPA-based SAMUL was chosen for fabricating inverted PSCs due to its highest crystallinity and hole mobility derived from the ordered H-aggregation, which resulted in a remarkably high fill factor of 86.45%. This enables a very impressive power conversion efficiency (PCE) of 26.07% to be achieved along with excellent device stability (94% of its initial PCE retained after continuous operation for 1200 h under 1-sun irradiation at maximum power point at 65°C). Additionally, a record-high PCE of 23.50% could be achieved by adopting a thermally evaporated SAMUL. This greatly simplifies and broadens the scope for SAM to be used for large-area devices on diverse substrates.

Exploring the Charge-Transport and Optical Characteristics of Organic Doublet Radicals: A Theoretical and Experimental Study with Photovoltaic Applications.

Herein, we present a series of stable radicals containing a trityl carbon-centered radical moiety exhibiting interesting properties. The radicals demonstrate the most blue-shifted anti-Kasha doublet emission reported so far with high color purity (full width at half-maximum of 46 nm) and relatively high photoluminescence quantum yields of deoxygenated toluene solutions reaching 31%. The stable radicals demonstrate equilibrated bipolar charge transport with charge mobility values reaching 10-4 cm2/V·s at high electric fields. The experimental results in combination with the results of TD-DFT calculations confirm that the blue emission of radicals violates the Kasha rule and originates from higher excited states, whereas the bipolar charge transport properties are found to stem from the particularity of radicals to involve the same molecular orbital(s) in electron and hole transport. The radicals act as the efficient materials for interlayers, passivating interfacial defects and enhancing charge extraction in PSCs. Consequently, this leads to outstanding performance of PSC, with power conversion efficiency surpassing 21%, accompanied by a remarkable increase in open-circuit voltage and exceptional stability.

Design, Synthesis, and Photophysical Characterization of Biocompatible Thermally Activated Delayed Fluorescent Carbazole-Coumarins for Sensing Applications.

A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been designed and synthetized using computer-aided density functional theory calculations. The TADF characteristics of the carbazole-coumarins were systematically explored both in solution and in the solid state, utilizing poly(methyl methacrylate) (PMMA) as a matrix. The study revealed that the introduction of carbazole units onto the coumarin benzene ring led to compounds with thermally induced reverse intersystem crossing and delayed fluorescence. The study further demonstrated the potential utility of these compounds in practical applications by incorporating them into a Cmr-PMMA-based sensor for molecular oxygen detection. The resulting sensor exhibited promising performance, highlighting the adaptability and efficacy of the synthesized TADF-carbazole-coumarin compounds for reversible molecular oxygen sensing.

Open and Closed Cage Silsesquioxane Dimers.

Polyhedral oligomeric silsesquioxane (POSS) is an organic-inorganic hybrid molecule with two structural variations, closed- and open-cage configurations, referred to as completely condensed POSS (CC-POSS) and corner-opened POSS (CO-POSS), respectively. In this study, we synthesized 12 dimers by combining CC- and CO-POSS variants decorated with isobutyl or phenyl substituents to explore their structure-property relationships. The choice of substituents, both at the cage vertices and open sites, significantly affected the thermal and optical properties of the materials. Modifying the substituents on CO- and CC-POSS, which are isomers, led to significant alterations in the material properties. Notably, isomer-bearing carbazole substituents exhibited a substantially higher quantum yield (0.32) than its counterpart isomer (0.13), underscoring the crucial role of structural nuances in determining material performance. These results offer valuable insights for the design of novel silsesquioxane-based materials.

Design of Thermally Activated Delayed Fluorescence Materials: Transition from Carbonyl to Amide-Based Acceptors.

Benzophenone skeletons containing a carbonyl unit (O=C) have been widely used as electron acceptors in the thermally activated delayed fluorescence (TADF) materials. Herein, we present a novel molecular design concept for TADF materials by transitioning from a carbonyl to an amide (O=C-N) skeleton as the acceptor. The amide unit, compared to its carbonyl counterpart, offers a more stable electronic configuration. Leveraging this insight, we have developed a series of high-performance TADF molecules based on benzoyl carbazole and carbazoline acceptors. These molecules exhibit exceptionally small singlet-triplet energy gaps and pronounced aggregation-enhanced emission properties, achieving photoluminescence quantum yields in neat films as high as 99%. Consequently, these materials serve as efficient emitters in non-doped organic light-eimtting diodes (OLEDs), reaching a maximum quantum efficiency (EQEmax) of up to 26.0%, significantly higher than the 17.0% obtained with benzophenone acceptor-based TADF molecules. Additionally, they have been used as TADF hosts in narrowband red fluorescent OLEDs, setting a record-high EQEmax of 22.4%.

Light Sensing beyond Vision: Focusing on a Possible Role for the FICZ/AhR Complex in Skin Optotransduction.

Although our skin is not the primary visual organ in humans, it acts as a light sensor, playing a significant role in maintaining our health and overall well-being. Thanks to the presence of a complex and sophisticated optotransduction system, the skin interacts with the visible part of the electromagnetic spectrum and with ultraviolet (UV) radiation. Following a brief overview describing the main photosensitive molecules that detect specific electromagnetic radiation and their associated cell pathways, we analyze their impact on physiological functions such as melanogenesis, immune response, circadian rhythms, and mood regulation. In this paper, we focus on 6-formylindolo[3,2-b]carbazole (FICZ), a photo oxidation derivative of the essential amino acid tryptophan (Trp). This molecule is the best endogenous agonist of the Aryl hydrocarbon Receptor (AhR), an evolutionarily conserved transcription factor, traditionally recognized as a signal transducer of both exogenous and endogenous chemical signals. Increasing evidence indicates that AhR is also involved in light sensing within the skin, primarily due to its ligand FICZ, which acts as both a chromophore and a photosensitizer. The biochemical reactions triggered by their interaction impact diverse functions and convey crucial data to our body, thus adding a piece to the complex puzzle of pathways that allow us to decode and elaborate environmental stimuli.

Carbazole Derivatives Binding to Bcl-2 Promoter Sequence G-quadruplex.

In this study, we used ultraviolet-visible (UV-Vis), fluorescence, and circular dichroism (CD) techniques, as well as molecular modeling, to probe the interactions between carbazole derivatives and the G-quadruplex structure formed in the promoter region of gene Bcl-2. This gene is a rational target for anticancer therapy due to its high expression in a variety of tumors as well as resistance to chemotherapy-induced apoptosis. We employed a sequence with a specific dual G-to-T mutation that may form a mixed-type hybrid G-quadruplex structure in the Bcl-2 P1 promoter region. The three tested carbazole compounds differing in substitution on the nitrogen atom of carbazole interact with the Bcl-2 G-quadruplex by the same binding mode with the very comparable binding affinities in the order of 105 M-1. During absorption and fluorescence measurements, large changes in the ligand spectra were observed at higher G4 concentrations. The spectrophotometric titration results showed a two-step complex formation between the ligands and the G-quadruplex in the form of initial hypochromicity followed by hyperchromicity with a bathochromic shift. The strong fluorescence enhancement of ligands was observed after binding to the DNA. All of the used analytical techniques, as well as molecular modeling, suggested the π-π interaction between carbazole ligands and a guanine tetrad of the Bcl-2 G-quadruplex. Molecular modeling has shown differences in the interaction between each of the ligands and the tested G-quadruplex, which potentially had an impact on the binding strength.

Investigating the potential of monocyclic B9N9 and C18 rings for the electrochemical sensing, and adsorption of carbazole-based anti-cancer drug derivatives: DFT-based first-principle study.

CONTEXT: For the first time, the use of monocyclic rings C18 and B9N9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C18 and B9N9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C18 and B9N9 rings of the complexes. METHODS: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B9N9, MKN@B9N9, MRY@B9N9, and THC@B9N9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C18, MKN@C18, MRY@C18, and THC@C18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B9N9 and C18, the analyte recovery time for C18 is much shorter (9.91 × 10-11 for THC@C18) than that for B9N9 shorter recovery time value of 3.75 × 10-9 for EPT@B9N9. These results suggest that our reported sensors B9N9 and C18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B9N9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications.

New Butterfly-Shaped Naphthalimide-Based AIE Gens: Synthesis and Photophysical Properties.

Two novel naphthalimide derivatives PTZNI-Cz and PTZNI-TPA were successfully designed and synthesized, in which phenothiazine, triphenylamine and carbazole were used as electron donors and naphthalimide was used as the electron acceptor. Their photophysical, electrochemical, and thermal properties were investigated. These derivatives showed remarkable aggregation-induced emission (AIE) effect. Furthermore, the maximum emission peaks of PTZNI-Cz and PTZNI-TPA in the thin film state are at 610 nm and 623 nm respectively, which is typical of red fluorescent materials.

Impact of Anchoring Groups on the Photocatalytic Performance of Iridium(III) Complexes and Their Toxicological Analysis.

Three different iridium(III) complexes, labelled as Ir1-Ir3, each bearing a unique anchoring moiety (diethyl [2,2'-bipyridine]-4,4'-dicarboxylate, tetraethyl [2,2'-bipyridine]-4,4'-diylbis(phosphonate), or [2,2'-biquinoline]-4,4'-dicarboxylic acid), were synthesized to serve as photosensitizers. Their electrochemical and photophysical characteristics were systematically investigated. ERP measurements were employed to elucidate the impact of the anchoring groups on the photocatalytic hydrogen generation performance of the complexes. The novel iridium(III) complexes were integrated with platinized TiO2 (Pt-TiO2) nanoparticles and tested for their ability to catalyze hydrogen production under visible light. A H2 turnover number (TON) of up to 3670 was obtained upon irradiation for 120 h. The complexes with tetraethyl [2,2'-bipyridine]-4,4'-diylbis(phosphonate) anchoring groups were found to outperform those bearing other moieties, which may be one of the important steps in the development of high-efficiency iridium(III) photosensitizers for hydrogen generation by water splitting. Additionally, toxicological analyses found no significant difference in the toxicity to luminescent bacteria of any of the present iridium(III) complexes compared with that of TiO2, which implies that the complexes investigated in this study do not pose a high risk to the aquatic environment compared to TiO2.

Mechanism of 7H-Dibenzo[c,g]carbazole metabolism in cytochrome P450 1A1: Insights from computational studies.

7H-Dibenzo[c,g]carbazole (DBC) is a prevalent environmental contaminant that induces tumorigenesis in several experimental animals. Recently, it has been utilized to develop high-performance solar cells and organic phosphorescent materials. It is imperative to strengthen investigations of DBC metabolism to understand its potential risks to human health. In this study, human CYP1A1 was employed as the metabolic enzyme to investigate the metabolic mechanism of DBC by molecular docking, molecular dynamics (MD) simulation, and quantum mechanical (QM) calculation. The results indicate that DBC binds to CYP1A1 in two modes (mode 1 and mode 2) mainly through nonpolar solvation energies (ΔGnonpolar). The formation of the two binding modes is attributed to the anchoring effect of the hydrogen bond formed by DBC with Asp320 (mode 1) or Ser116 (mode 2). Mode 1 is a "reactive" conformation, while mode 2 is not considered a "reactive" conformation. C5 is identified as the dominant site, and the pyrrole nitrogen cannot participate in the metabolism. DBC is metabolized mainly by a distinct electrophilic addition-rearrangement mechanism, with an energy barrier of 21.74 kcal/mol. The results provide meaningful insights into the biometabolic process of DBC and contribute to understanding its environmental effects and health risks.

Effects of carbazolyl and diphenylamino substituents bearing methoxy groups on the performance of hole-transporting materials in OLEDs.

Newly designed and synthesized derivatives of pentaphenylbenzene with methoxy-substituted carbazolyl or diphenylamino moieties were investigated to estimate their applicability as hole transport materials. Both the compounds exhibit high thermal stability. The intramolecular charge transfer is blocked for the film of the compound containing diphenylamino groups. The intermolecular charge transfer is induced in the film of carbazolyl-containing compound. The derivative of pentaphenylbenzene and diphenylamine exhibits higher hole drift mobility (2.4·10-3 cm2/V·s at the electric field of 5.5·105 V/cm) and by 0.1 eV lower ionization potential than the carbazolyl-containing compound. Both the compounds were utilized as hole-transporting materials in a series of organic light emitting diodes (OLEDs) based on of thermally activated delayed fluorescence. With the maximum values of external quantum efficiency of 25.9 % and power efficiency of 43.4 lm/W, OLEDs containing the layers of the synthesized compounds outperformed the device based on TCTA by 4 %, without the change in spectral properties. Variable angle spectroscopic ellipsometry revealed the moderate average roughness of the films of the compound deposited by the thermal vacuum evaporation technique with an arithmetic mean deviation of not more than 0.8 nm. The prominent hole transport characteristics of the compounds make them good candidates for utilization in optoelectronic devices.

Isolation and characterization of feruloylated oligosaccharides from Phyllostachys acuta and in vitro antioxidant activity.

Feruloylated oligosaccharides (FOs) generated by decomposing plant hemicellulose, offer a wide range of potential applications in both the food and biomedical areas. As a graminaceous plant, bamboo is rich in hemicellulose. However, the structural composition and activity studies of FOs from it were rarely reported. In this study, FOs from Phyllostachys acuta (pFOs) obtained by enzymatic hydrolysis were isolated by AmberliteXAD-2 and C18 SPE columns. Then, pFOs were qualitatively and quantitatively analyzed by UPLC-ESI-MS/MS after labeled by 3-Amino-9-ethyl-carbazole (AEC), and the chemical antioxidant activity of pFOs and effects of pFOs on H2O2-induced oxidative damage were investigated. Finally, 14 of pFOs isomers were distinguished and identified, of which 10 did not contain hexoses and 4 did, and the three most abundant pFO structures were 12 (Iso 7, F1A1X2H2-AEC, 29.04 %), 11 (Iso 6, F1A1X1H2-AEC, 17.96 %), and 4 (Iso 3-1, F1A1X3-AEC, 15.57 %). The results of antioxidant studies showed that pFOs possessed certain reducing power, scavenging DPPH radicals, scavenging superoxide anion radicals, and scavenging hydroxyl radicals. Among them, the ability to clear DPPH radicals was particularly significant. pFOs significantly reduced the viability of RAW264.7 cells after H2O2 induction, whereas pFOs had a significant protective effect (p < 0.001). pFOs increased the viability of T-AOC and SOD enzymes in oxidatively damaged cells, as well as had a significant inhibition effect on ROS elevation (p < 0.001). This study lays the foundation for the structural analysis and antioxidant activity evaluation of bamboo-derived feruloyl oligosaccharides for their application in food and pharmaceutical fields.

Novel carbazole-oxadiazole derivatives as anti-α-glucosidase and anti-α-amylase agents: Design, synthesis, molecular docking, and biological evaluation.

To find novel inhibitors of α-glucosidase and α-amylase, a series of new carbazole-oxadiazole derivatives (6a-6n) were prepared, and screened for their anti-α-glucosidase and anti-α-amylase effects. Most of the tested derivatives showed different degrees of α-glucosidase and α-amylase inhibitory activity (IC50: 21.39 ± 0.69-92.05 ± 1.54 µM, 45.53 ± 1.50-126.14 ± 6.33 µM, respectively) compared to the standard acarbose (IC50: 427.00 ± 9.56 µM, 24.68 ± 1.10 µM, respectively). Thereinto, 6c (IC50 = 21.39 ± 0.69 µM) displayed the most effective anti-α-glucosidase activity and 6e presented the best anti-α-amylase activity with an IC50 value of 45.53 ± 1.50 µM. Lineweaver-Burk plot analysis suggested that 6c and 6e behaved as mixed α-glucosidase inhibitor and mixed α-amylase inhibitor, respectively. The results of circular dichroism, atomic force microscope, and molecular docking simulation exposed interaction mechanisms between two preferred compounds (6c and 6e) and their corresponding enzymes. Combined with the possible properties of reducing the elevation in postprandial blood glucose, oral activity, positive bioavailability, and low cytotoxicity of 6c and 6e, it could be concluded that the target derivatives may be able to act as lead molecules for the development of new hypoglycemic agents.

Structure-activity relationship study of new carbazole sulfonamide derivatives as anticancer agents with dual-target mechanism.

A series of novel carbazole sulfonamide derivatives were synthesized and evaluated for antiproliferative activity. Among them, compounds 7 and 15 showed strong potency (IC50 values of 0.81-31.19 nM) against five different cancer cells including multidrug-resistant MCF7/ADR cells. Compound 15 displayed a high cancer cell selectivity (IC50(L02)/average IC50: SI = 7.7). The l-valine prodrug 7a and the phosphate prodrug 15a exerted rohust in vivo antitumor efficacies and accepted safety prolifes. Further mechanism studies revealed that 7 and 15 directly bind to the colchicine site in tubulin to block tubulin polymerization, promote microtubule fragmentation at the cellular level, and induce apoptosis with G2/M cell cycle arrest. These compounds also inhibit HEMC-1 cells migration and vascular tube formation. Additionally, compound 7 displayed a selective inhibition of Topo I. Collectively, these studies suggest that 7 and 15 represents a promising new generation of tubulin inhibitors for cancer treatment.

A Ratiometric Green Fluorescent Carbazole-Bis(hydrazinobenzothiazole) Probe for the Selective Detection of Toxic Hg2+ Ions in Real Water Samples.

A dyad Carbazolyl-bis(hydrazinobenzothiazole) was designed to form a symmetrical structure that containing two-arm active binding sites facilitates coordination with Hg2+ ion. This sensor has imparted a colorimetric and fluorometric changes in presence of Hg2+ ions. The ligand showed a selective blue shift in presence of Hg2+even in co-existence with heavy metal ions with luminescence change from colorless to blue and colorless to green under day light. Enhanced Intramolecular charge transfer process is responsible for fluorescence transformation when ligand interacts with Hg2+ ion. The emission spectra showed a ratiometric response to increasing addition of Hg2+ ions. The sensor is capable of detecting above the lower concentration of 6.8025×10-8 M. The fluorescence efficiency of CBT-2 with Hg2+ ion is quite stable under different co-metal ions and wide range of pH 6 to 9. The sensor CBT-2 forms a 1 : 1 stoichiometric complex with Hg2+ ions and the binding nature is confirmed from the 1H-NMR, FTIR, and mass spectroscopic studies. The sensor CBT-2 and its Hg2+ complex possess good binding nature to protein in Bovine Serum Albumin which could be good in biological applications. Additionally, wedevelop a practical application in real water sample analysis and electrochemical detection via oxidation potential discrimination.

Direct Comparative Studies Revealing the Contribution of TADF Activity of Organic Emitters Towards Efficient Electrochemiluminescence.

Electrochemiluminescence (ECL) featuring thermally activated delayed fluorescence (TADF) properties has attracted considerable interest, showcasing their potential for 100 % exciton harvesting, which marks a significant advancement in the realm of organic ECL. However, the challenge of elucidating the precise contribution of TADF to the enhanced ECL efficiency arises due to the lack of comparative studies of organic compounds with or without efficient TADF properties. In this study, we present four carbazole-benzonitrile molecules possessing similar chemical structures and comparable exchange energy (ΔEST). Despite their comparable properties, these compounds exhibited varying TADF efficiencies, warranting a closer examination of their underlying structural and electronic characteristics governing the optical properties. Consequently, intense ECL emission was only observed from 4CzBN with a remarkable TADF efficiency, underscoring the substantial difference in the ECL signal among molecules with comparable ΔEST and similar spectral properties but varying TADF activity.

Predicting anti-trypanosome effect of carbazole-derived compounds by powerful SVM with novel kernel function and comprehensive learning PSO.

In order to predict the anti-trypanosome effect of carbazole-derived compounds by quantitative structure-activity relationship, five models were established by the linear method, random forest, radial basis kernel function support vector machine, linear combination mix-kernel function support vector machine, and nonlinear combination mix-kernel function support vector machine (NLMIX-SVM). The heuristic method and optimized CatBoost were used to select two different key descriptor sets for building linear and nonlinear models, respectively. Hyperparameters in all nonlinear models were optimized by comprehensive learning particle swarm optimization with low complexity and fast convergence. Furthermore, the models' robustness and reliability underwent rigorous assessment using fivefold and leave-one-out cross-validation, y-randomization, and statistics including concordance correlation coefficient (CCC), [Formula: see text] , [Formula: see text] , and [Formula: see text] . Among all the models, the NLMIX-SVM model, which was established by support vector regression using a nonlinear combination of radial basis kernel function, sigmoid kernel function, and linear kernel function as a new kernel function, demonstrated excellent learning and generalization abilities as well as robustness: [Formula: see text] = 0.9581, mean square error (MSE) = 0.0199 for the training set and [Formula: see text] = 0.9528, MSE = 0.0174 for the test set. [Formula: see text] , [Formula: see text] , CCC, [Formula: see text] , [Formula: see text], and [Formula: see text] are 0.9539, 0.8908, 0.9752, 0.9529, 0.9528, and 0.9633, respectively. The NLMIX-SVM method proved to be a promising way in quantitative structure-activity relationship research. In addition, molecular docking experiments were conducted to analyze the properties of new derivatives, and a new potential candidate drug molecule was ultimately found. In summary, this study will provide help for the design and screening of novel anti-trypanosome drugs.

Design and Application of Cu2+ Fluorescent Sensor Based on Carbazole Derivatives.

A novel fluorescent sensor for the detection of Cu2+ was developed based on carbazole derivatives. After the addition of Cu2+, the sensor exhibited obvious fluorescence quenching phenomenon, and the optical signal variation also enabled the sensor to quantitatively analyze Cu2+ due to the formation of a stable 1:1 metal-ligand complex in a short time. In addition, the sensor possessed chemical reversibility and pH stability. The cell imaging and zebra fish experiments also verified its application value in biological system.

Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents.

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.