The therapeutic value of bifidobacteria in cardiovascular disease.

There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products.

C-H functionalization of quinoline N-oxides catalyzed by Pd(II) complexes: a computational study.

Pd(II) catalysts, particularly the acetate salt in acetic acid, tended to favor regioselective C-H activation of quinoline N-oxides (QOs) at the C2 position. However, Pd(II)Cl2 was shown to catalyze their C-H activation at C8 and, in the presence of water, C8-H activation was accompanied by the formation of 2-quinolinones. The aim of the DFT study described in this work was to shed light on the complete mechanism of these competing catalytic reactions, when PdCl2 reacts with QO and benzaldehyde in dichloroethane. C-H activation of QO was the first step of the reaction and involved either a metallacycle, with a CQO-Pd(II) σ-bond and a C(8)-H-Pd(II) agostic bond, or an η3-QO complex, with three carbon atoms of the heteroring of QO binding PdCl2. The first situation led to the unusual C8 activation and the second to C2 activation. The σ-metallacycle undergoes C8-H activation and the energy of the TOF determining the transition state to form the product is ∼17 kcal mol-1, while for the reaction through the π-metallacycle (C2-H activation) the corresponding energy is higher (∼29 kcal mol-1) and thus is not competitive under the same conditions. The reaction proceeding through the σ-complex, activating the C8 position, is preferred, in agreement with experimental results. Both reactions involve oxidation of Pd(II) to Pd(IV) and the catalyst is regenerated. When small amounts of water are added to the reaction mixture, C8-H activation (acylation) results from the same σ-metallacycle with the same barrier, but the simultaneous formation of 2-quinolinones is more complicated. It starts with OH- attack at the C2 position, and is followed by the migration of two hydrogen atoms, and the final reductive elimination step ends with Pd(0). The higher barriers for the migration and reoxidation of Pd(0) are associated with the more demanding reaction conditions. The different reactivity of Pd(II)(OAc)2 under analogous conditions is clarified, as it is only capable of forming the above mentioned π-complex and thus of activating the C2 position of QO. This catalyst can preferentially activate the C8-H bond under rather different conditions, including in particular acetic acid medium, as shown by other authors.

Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants.

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.

Transition Metal-Controlled Divergent Annulations of Azomethine Imines with Iodonium Ylides via C-Centered [1,2]-Rearrangement.

Transition metal-controlled divergent annulation reactions of azomethine imines with iodonium ylides via C-centered [1,2]-rearrangement have been developed. The azomethine imino group, as a switchable and transient directing group (DG), underwent intramolecular nucleophilic addition and in situ generated bicyclic diaziridine, which facilitated the C-centered [1,2]-rearrangement and subsequent divergent annulations in the presence of different metal complexes as the catalysts. The benzo[c]chromen-1-one and pyrano[de]isochromene scaffolds could be independently constructed with Rh(III) and Ru(II), respectively. It was worth noting that the azomethine imino group was employed first as the switchable DG through rearrangement progress.

2-Butyne Biscarbonate as a "Bridge" in Rhodium(III)-Catalyzed [4 + 2] Cyclization and Diels-Alder Reaction.

Described herein is the development of an unprecedented approach to construct multiple heterocycles with high selectivity through Rh(III)-catalyzed two- or three-component cyclization reaction from simple and readily available starting materials: N-methoxybenzamides, 2-butyne biscarbonate, and maleimides. This methodology provides an efficient strategy for the synthesis of diverse and complicated heterocycles in a one-pot manner and displays excellent features of extremely mild reaction conditions, easy operation, excellent regioselectivity, and good functional group compatibility.

The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends.

Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed.

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect.

Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

TBAI-Catalysed Formal [4+4]-Cycloaddition: Easy Access to Oxa-Bridged Eight-Membered Heterocycles.

TBAI-catalysed [4+4]-cyclization reaction of anthranils with hydrazones to deliver oxa-bridged eight-membered heterocycles in accepted yields was developed. Preliminary mechanistic studies indicated that the reaction involved the in situ generation of vinyldiazenes from readily available hydrazones followed by an aza-Michael addition of the anthranil substrates onto the vinyldiazenes and subsequent annulation. This transformation involved the formation of two new C-N bonds and C-O bond in one pot, overcoming the synthetic limitations of anthranils in organic chemistry. This strategy benefits from high efficiency and atomic economy with mild reaction conditions.

Preparation and Evaluation of Curcumin Derivatives Nanoemulsion Based on Turmeric Extract and Its Antidepressant Effect.

Purpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect. Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted. Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration. Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.

Novel Curcumin Derivative-Decorated Ultralong-Circulating Paclitaxel Nanoparticles: A Novel Delivery System with Superior Anticancer Efficacy and Safety.

Purpose: Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods: PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results: The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, -33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T1/2, MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion: PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.

Lewis Acid-Catalyzed [3 + 2]-Cyclization of Iodonium Ylides with Azadienes: Access to Spiro[benzofuran-2,2'-furan]-3-ones.

A highly regioselective synthesis of spiro[benzofuran-2,2'-furan]-3-ones has been explored via Lewis acid-catalyzed [3 + 2] cyclization of iodonium ylides with azadienes. The acidity of the Lewis acid was significantly strengthened with strong hydrogen bond donors, thereby promoting the enolization isomerization of iodonium ylides for the subsequent cycloaddition. This reaction was compatible with a broad range of substrates under the mild reaction conditions, and efficiently delivered spiro-heterocycles with excellent stereoselectivity.

Latest research progress on anticancer effect of baicalin and its aglycone baicalein.

Cancer, which is a leading cause of deaths around the world, is characterized by genetic mutations and epigenetic changes. Baicalin and its aglycone baicalein, the major bioactive flavones derived from the dried root of Scutellaria baicalensis Georigi, belong to flavonoid compounds. Many studies demonstrated that both of them exhibited remarkable promising anticancer activities. This study summarized potential anticancer mechanisms of baicalin and baicalein including induction of apoptosis, initiation of cell cycle arrest, suppression of metastasis, induction of autophagy, and regulation of immunity. Combination strategies involving baicalin or baicalein as chemotherapeutic adjuvants, clinical trial and safety were also discussed. In addition, we compared the difference in their anticancer effects. Interestingly, baicalein showed quicker and stronger inhibitory effects on multiple cancers than those of baicalin, probably due to its smaller size and high lipophilicity which contribute to fast absorption and improve ability to penetrate cells. Taken together, both baicalin and baicalein are effective in treating cancer with good tolerance. However, deglycosylation of baicalin to baicalein was found to have stronger anticancer potential.

Formulation of the novel structure curcumin derivative-loaded solid lipid nanoparticles: synthesis, optimization, characterization and anti-tumor activity screening in vitro.

This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity in vitro. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (p < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.

Patient-Derived Xenograft: A More Standard "Avatar" Model in Preclinical Studies of Gastric Cancer.

Despite advances in diagnosis and treatment, gastric cancer remains the third most common cause of cancer-related death in humans. The establishment of relevant animal models of gastric cancer is critical for further research. Due to the complexity of the tumor microenvironment and the genetic heterogeneity of gastric cancer, the commonly used preclinical animal models fail to adequately represent clinically relevant models of gastric cancer. However, patient-derived models are able to replicate as much of the original inter-tumoral and intra-tumoral heterogeneity of gastric cancer as possible, reflecting the cellular interactions of the tumor microenvironment. In addition to implanting patient tissues or primary cells into immunodeficient mouse hosts for culture, the advent of alternative hosts such as humanized mouse hosts, zebrafish hosts, and in vitro culture modalities has also facilitated the advancement of gastric cancer research. This review highlights the current status, characteristics, interfering factors, and applications of patient-derived models that have emerged as more valuable preclinical tools for studying the progression and metastasis of gastric cancer.

Anti-lung cancer effect of paclitaxel solid lipid nanoparticles delivery system with curcumin as co-loading partner in vitro and in vivo.

The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-κB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.

Cobalt(II)-Catalyzed C-H and N-H Functionalization of 1-Arylpyrazolidinones with Dioxazolones as Bifunctional Synthons.

Dioxazolone has been attractive as an important synthon for a direct C-H amidation through a nitrene intermediate or Curtius rearrangement to form the isocyanate. However, the combination of two reaction models of dioxazolone has not been reported. Herein, a cobalt-catalyzed C-H and N-H functionalization of 1-arylpyrazolidinones with dioxazolones was developed. The dioxazolones acted as an amidated and carboxamidated reagent. Three C-N bonds were formed in a "one-pot" manner, which promoted the requirement of synthetic diversity.

The Effects of a Novel Curcumin Derivative Loaded Long-Circulating Solid Lipid Nanoparticle on the MHCC-97H Liver Cancer Cells and Pharmacokinetic Behavior.

Purpose: The objective of this study was to develop long-circulating solid lipid nanoparticles (LSLN) containing a novel curcumin (CU) derivative (CU1), to improve CU1's pharmacokinetic behavior and its anti-cancer effects in MHCC-97H liver cancer cells. Methods: LSLN loaded with CU1 (CU1-LSLN) was optimized and characterized. The cell biological properties and the anti-cancer mechanism of CU1-LSLN on MHCC-97H cells were evaluated by MTT, flow cytometry, Transwell, and Western blot. CU1-LSLN was further evaluated for pharmacokinetic behavior, biodistribution, and liver toxicity in SD rats. Results: The optimized CU1-LSLN formulation showed the ideal particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE%), and drug loading (DL%) of 122.10 ± 6.63 nm, 0.19 ± 0.02, -36.30 ± 1.25 mV, 94.98 ± 0.90% and 4.53 ± 0.69%, respectively. X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrometry (FTIR) indicated that CU1 was well encapsulated by LSLN and existed in amorphous form. Storage stability of CU1-LSLN was up to 180 days with a sustained-release of drug over 96 h. The uptake efficiency of CU1-LSLN to MHCC-97H cells was 3.24 and 2.98 times higher than that of CU and CU1 after treatment for 3 h, which helped to enhance the inhibitive effect of CU1-LSLN on the proliferation, migration, and invasion potential of MHCC-97H cells and increased its ability to promote apoptosis. Meanwhile, the expression levels of NF-κB, COX-2, MMP-2, MMP-9, and uPA decreased significantly. In vivo, CU1-LSLN prolonged the retention time of the drug, the area under the curve (AUC) increased significantly (CU: 69.9-fold, CU1: 85.9-fold), and no significant liver toxicity was observed. Conclusion: CU1-LSLN is a novel preparation with great potential for treating liver cancer.

Rh(III)-Catalyzed Synthesis of Indazolo[2,3-a]quinolines: Vinylene Carbonate as C1 and C2 Building Blocks.

A rhodium-catalyzed cyclization of azobenzenes and vinylene carbonate via C-H bond activation to construct indazolo[2,3-a]quinolines has been developed. This protocol offers an efficient method for synthesis of the titled products in good yields with broad functional group tolerance. In this reaction, three C-C bonds and C-N bond are formed in one pot, and vinylene carbonate (VC) acts as C1 and C2 synthons as well as "vinylene transfer" agent and acylation reagent in the construction of target-fused heterocycles. Moreover, the products exhibit favorable fluorescence properties, which indicate their potential application as fluorescent materials and biosensors.

Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo.

CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

Novel Ferrocene Derivatives Induce Apoptosis through Mitochondria-Dependent and Cell Cycle Arrest via PI3K/Akt/mTOR Signaling Pathway in T Cell Acute Lymphoblastic Leukemia.

T cell acute lymphoblastic leukemia (T-ALL) is one of the most common causes of death in pediatric malignancies. However, the clinical chemotherapy for T-ALL has been limited by numerous side effects, emphasizing that novel anti-T-ALL drugs are urgently needed. Herein, a series of 2-acyl-1-dimethylaminomethyl-ferrocenes for cancer therapy have been evaluated. Among them, F1 and F3 exhibited potent cytotoxicity against T-ALL cell lines, especially Jurkat cells, with low cytotoxicity for normal cells. Further mechanistic studies revealed that F1 and F3 could induce apoptosis in Jurkat cells by destructing mitochondrial membrane, enhancing reactive oxygen species (ROS) generation, decreasing the Bcl-2/Bax ratio, releasing Cytochrome c, and increasing the expression of Cleaved Caspase-9/-3 and Cleaved PARP. Additionally, F1 and F3 could suppress cell proliferation and arrest the cell cycle at G0/G1 phase through the PI3K/Akt/mTOR signaling pathway by down-regulating the expression of CDK6, Cyclin D1, p-Akt, p-GSK-3ß, p-mTOR, p-p70 S6K, and up-regulating the expression of P21 and P27, which would also be a possible mechanism. Consequently, ferrocene derivatives F1 and F3 could induce apoptosis through a mitochondria-dependent pathway mediated by ROS, and cell cycle arrest at G0/G1 phase via the PI3K/Akt/mTOR signaling pathway in Jurkat cells. The present study provided fundamental insights into the clinical application of F1 and F3 for the treatment of T-ALL.