Myricetin-Loaded Nanomicelles Protect against Cisplatin-Induced Acute Kidney Injury by Inhibiting the DNA Damage-cGAS-STING Signaling Pathway.

Acute kidney injury (AKI) is the most common side effect of the anti-cancer drug cisplatin, and currently, no effective preventive measures are available in clinical practice. Oxidative stress and DNA damage mechanisms may be involved in cisplatin-induced AKI. In this study, we prepared Kolliphor HS15-based myricetin-loaded (HS15-Myr) nanomicelles and explored the mechanism of protection against cisplatin-induced AKI. In vitro results showed that the HS15-Myr nanomicelles enhanced the antioxidant activity of myricetin (Myr) and inhibited cisplatin-induced proliferation inhibition of HK-2 cells. Moreover, the HS15-Myr nanomicelles inhibited cisplatin-induced reactive oxygen species accumulation, mitochondrial membrane potential reduction, and DNA damage, which might be related to the inhibition of the cyclic GMP-AMP synthase (cGAS)─stimulating interferon gene (STING) signaling pathway. In vivo results in mice showed that the significant reductions in body weight and renal indices and the increased blood urea nitrogen and serum creatinine levels induced by cisplatin could be significantly reversed by pretreating with the HS15-Myr nanomicelles. Furthermore, nanomicelle pretreatment significantly altered the activities of antioxidant enzymes (e.g., GSH, MDA, and SOD) induced by cisplatin. In addition, cisplatin-induced inflammatory responses in mouse kidney tissue were found to be inhibited by pretreatment with HS15-Myr nanomicelles, such as IL-1ß and TNF-α expression. The nanomicelles also significantly inhibited cisplatin-induced activation of the DNA damage-cGAS-STING pathway in kidney tissues. Together, our findings suggest that Myr-loaded nanomicelles are potential nephroprotective drugs.

Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury.

Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

New Pyrroline Isolated from Antarctic Krill-Derived Actinomycetes Nocardiopsis sp. LX-1 Combining with Molecular Networking.

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a-p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2-12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a-p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.

Bioactivity-Guided Screening of Antimicrobial Secondary Metabolites from Antarctic Cultivable Fungus Acrostalagmus luteoalbus CH-6 Combined with Molecular Networking.

With the increasingly serious antimicrobial resistance, discovering novel antibiotics has grown impendency. The Antarctic abundant microbial resources, especially fungi, can produce unique bioactive compounds for adapting to the hostile environment. In this study, three Antarctic fungi, Chrysosporium sp. HSXSD-11-1, Cladosporium sp. HSXSD-12 and Acrostalagmus luteoalbus CH-6, were found to have the potential to produce antimicrobial compounds. Furthermore, the crude extracts of CH-6 displayed the strongest antimicrobial activities with 72.3-84.8% growth inhibition against C. albicans and Aeromonas salmonicida. The secondary metabolites of CH-6 were researched by bioactivity tracking combined with molecular networking and led to the isolation of two new α-pyrones, acrostalapyrones A (1) and B (2), along with one known analog (3), and three known indole diketopiperazines (4-6). The absolute configurations of 1 and 2 were identified through modified Mosher's method. Compounds 4 and 6 showed strong antimicrobial activities. Remarkably, the antibacterial activity of 6 against A. salmonicida displayed two times higher than that of the positive drug Ciprofloxacin. This is the first report to discover α-pyrones from the genus Acrostalagmus, and the significant antimicrobial activities of 4 and 6 against C. albicans and A. salmonicida. This study further demonstrates the great potential of Antarctic fungi in the development of new compounds and antibiotics.

Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene, which is involved in the RAS/MAPK cell signaling transduction process. SHP2 has been shown to contribute to the progression of various cancers and is emerging as an important target for anti-tumor drug research. However, past efforts to develop SHP2 inhibitors into drugs have been unsuccessful owing to the positively charged nature of the active site pocket tending to bind negatively charged groups that are usually non-drug-like. Here, a series of uncharged pyrazoline derivatives were designed and developed as new SHP2 inhibitors using a structure-based strategy. Compound 4o, which exhibited the strongest SHP2 inhibitory activity, bound directly to the catalytic domain of SHP2 in a competitive manner through multiple hydrogen bonds. Compound 4o affected the RAS/MAPK signaling pathway by inhibiting SHP2, and subsequently induced apoptosis and growth inhibition of HCT116 cells in vitro and in vivo. Notably, the oral administration of compound 4o in large doses showed no obvious toxicity. In summary, our findings provide a basis for the further development of compound 4o as a safe, effective and anti-tumor SHP2 inhibitor.

Highly E-Selective Synthesis of α-Fluoro-ß-arylalkenyl Sulfones from gem-Difluoroalkenes with Sodium Sulfinates.

The straightforward synthesis of α-fluoro-ß-arylalkenyl sulfones under transition-metal- and base-free conditions has been described, which displays broad functional group compatibility and high stereoselectivity. In particular, the strategy is also applied to the late-stage modification of complex natural products and drugs.

New Polyketides from the Antarctic Fungus Pseudogymnoascus sp. HSX2#-11.

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus with a ubiquitous distribution in Antarctica. Meanwhile, the study of its secondary metabolites is infrequent. Systematic research of the metabolites of the fungus Pseudogymnoascus sp. HSX2#-11, guided by the method of molecular networking, led to the isolation of one novel polyketide, pseudophenone A (1), along with six known analogs (2-7). The structure of the new compound was elucidated by extensive spectroscopic investigation and single-crystal X-ray diffraction. Pseudophenone A (1) is a dimer of diphenyl ketone and diphenyl ether, and there is only one analog of 1 to the best of our knowledge. Compounds 1 and 2 exhibited antibacterial activities against a panel of strains. This is the first time to use molecular networking to study the metabolic profiles of Antarctica fungi.

Nitrogenous Compounds from the Antarctic Fungus Pseudogymnoascus sp. HSX2#-11.

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one new pyridine derivative, 4-(2-methoxycarbonyl-ethyl)-pyridine-2-carboxylic acid methyl ester (1), together with one pyrimidine, thymine (2), and eight diketopiperazines, cyclo-(dehydroAla-l-Val) (3), cyclo-(dehydroAla-l-Ile) (4), cyclo-(dehydroAla-l-Leu) (5), cyclo-(dehydroAla-l-Phe) (6), cyclo-(l-Val-l-Phe) (7), cyclo-(l-Leu-l-Phe) (8), cyclo-(l-Trp-l-Ile) (9) and cyclo-(l-Trp-l-Phe) (10). The structures of these compounds were established by extensive spectroscopic investigation, as well as by detailed comparison with literature data. This is the first report to discover pyridine, pyrimidine and diketopiperazines from the genus of Pseudogymnoascus.

Palladium-Catalyzed Remote C-H Phosphonylation of Indoles at the C4 and C6 Positions by a Radical Approach.

Palladium-catalyzed direct C-H activation of indole benzenoid moiety has been achieved in the past decade. However, palladium-catalyzed remote C-H activation of indoles is rare. Herein, we report a challenging palladium-catalyzed remote C4-H phosphonylation of indoles by a radical approach. The method provides access to a series of C4-phosphonylated indoles, including tryptophan and tryptophan-containing dipeptides, which are typically inaccessible by direct C4-H activation due to its heavy reliance on C3 directing groups. Notably, unexpected C6-phosphonylated indoles were obtained through blocking of the C4 position. The preliminary mechanistic studies indicated that the reactions may proceed via a C7-palladacycle/remote-activation process. Based on the strategy, examples of remote C4-H difluoromethylation with BrCF2 COOEt are also presented, suggesting that the strategy may offer a general blueprint for other cross-couplings.

16S rRNA Sequencing and Metagenomics Study of Gut Microbiota: Implications of BDB on Type 2 Diabetes Mellitus.

Gut microbiota has a critical role in metabolic diseases, including type 2 diabetes mellitus (T2DM). 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a natural bromophenol isolated from marine red alga Rhodomela confervoides. Our latest research showed that BDB could alleviate T2DM in diabetic BKS db mice. To find out whether BDB modulates the composition of the gut microbiota during T2DM treatment, 24 BKS db diabetic mice were randomly grouped to receive BDB (n = 6), metformin (n = 6), or the vehicle (n = 6) for 7 weeks in a blinded manner. Non-diabetic BKS mice (n = 6) were used as normal control. Diabetic mice treated with BDB or metformin demonstrated significant reductions in fasting blood glucose (FBG) levels compared with the vehicle-treated mice in the 7th week. Pyrosequencing of the V3-V4 regions of the 16S rRNA gene revealed the changes of gut microbiota in response to BDB treatment. The result demonstrated short-chain acid (SCFA) producing bacteria Lachnospiraceae and Bacteroides were found to be significantly more abundant in the BDB and metformin treated group than the vehicle-treatment diabetic group. Remarkably, at the genus levels, Akkermansia elevated significantly in the BDB-treatment group. Metagenomic results indicated that BDB may alleviate the metabolic disorder of diabetic mice by promoting propanoate metabolism and inhibiting starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism. In conclusion, our study suggests that the anti-diabetic effect of BDB is closely related to the modulating structure of gut microbiota and the improvement of functional metabolism genes of intestinal microorganisms.

CYC31, A Natural Bromophenol PTP1B Inhibitor, Activates Insulin Signaling and Improves Long Chain-Fatty Acid Oxidation in C2C12 Myotubes.

3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga Rhodomela confervoides. Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was embedded into the catalytic pocket of PTP1B. A cellular study found that CYC31 increased the activity of insulin signaling and promoted 2-NBDG uptake through GLUT4 translocation in C2C12 myotubes. Further studies showed that CYC31 ameliorated palmitate-induced insulin resistance in C2C12 myotubes. Moreover, CYC31 treatment significantly increased the mRNA expression of carnitine palmitoyltransferase 1B (CPT-1B) and fatty acid binding protein 3 (FABP3), which was tightly linked with fatty acid oxidation. These findings suggested that CYC31 could prevent palmitate-induce insulin resistance and could improve fatty acid oxidation through PTP1B inhibition.

The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by Promoting Apoptosis, Regulating the MAPK Pathway and Inducing Mitochondrial Dysfunction.

Triple negative breast cancer (TNBC) is the most aggressive cancer in women, and despite improved treatments, it remains a major cause of morbidity and mortality. We and others have demonstrated that different hybrid compounds targeting PARP/MAPK or other pathways to inhibit cancer progression may lead to promising therapeutic results. We introduced fluorine to alter the physical properties of the compounds. TSC-3C was one of the generated compounds. Upon treatment with TSC-3C, MDA-MB-231 cell proliferation, invasion, and migration were inhibited. TSC-3C induced MDA-MB-231 cell mitochondrial dysfunction and apoptosis, which may be caused by reducing the level of phosphorylated p44/42 MAPK (ERK1/2) and increasing the level of p-JNK. The present study may help to elucidate the role of the MAPK pathway in the development of breast cancer and may promote further research on halogenated heterocyclic compounds for the treatment of breast cancer.

Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2',3,3'-Tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice.

Protein tyrosine phosphatase 1B (PTP1B) is a widely confirmed target of the type 2 diabetes mellitus (T2DM) treatment. Herein, we reported a highly specific PTP1B inhibitor 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (compound 1), which showed promising hypoglycemic activity in diabetic BKS db mice. With the IC50 value of 2.4 µM, compound 1 could directly bind to the catalytic pocket of PTP1B through a series of hydrogen bonds. Surface plasmon resonance analysis revealed that the target affinity [KD (equilibrium dissociation constant) value] of compound 1 binding to PTP1B was 2.90 µM. Moreover, compound 1 could activate the insulin signaling pathway in C2C12 skeletal muscle cells. We further evaluated the long-term effects of compound 1 in diabetic BKS db mice. Notably, oral administration of compound 1 significantly reduced the blood glucose levels of diabetic mice with increasing insulin sensitivity. In addition, the dyslipidemia of diabetic mice was also significantly improved by compound 1 gavage. The histological experiments showed that compound 1 treatment significantly ameliorated the disordered hepatic and pancreatic architecture and increased the glycogen content in the liver tissues as well as improved the insulin secretion function of pancreas. Taken together, our results manifested that the natural product compound 1 was a highly specific PTP1B inhibitor, which could activate insulin signaling pathway and ameliorate hyperglycemia and dyslipidemia in diabetic BKS db mice.

CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs.

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found that CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27 effectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC) and triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased insulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to systemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was performed to investigate global changes in phosphorylation. Enriched GO annotation showed that most regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG analysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27 treatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of mRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our results suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the insulin signaling pathways and modulating RNA splicing-associated RBPs.

Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents Through ROS-Mediated Apoptotic Pathway.

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2-18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.

Design and Synthesis of a Fluorescent Probe with a Large Stokes Shift for Detecting Thiophenols and Its Application in Water Samples and Living Cells.

A turn-on florescent probe (probe-KCP) was developed for highly selective detection of thiophenols based on a donor-excited photo-induced electron transfer mechanism. Herein, the synthesis of the probe, a chalcone derivative, through a simple straightforward combination of a carbazole-chalcone fluorophore with a 2,4-dinitrophenyl functional group. In a kinetic study of the probe-KCP for thiophenols, the probe displayed a short response time (~30 min) and significant fluorescence enhancement. In selection and competition experiments, the probe-KCP exhibited excellent selectivity for thiophenols over glutathione (GSH), cysteine (Cys), sodium hydrosulfide (NaSH), and ethanethiol (C2H5SH) in addition to common anions and metal ions. Using the designed probe, we successfully monitored and quantified thiophenols, which are highly toxic. This turn-on fluorescence probe features a remarkably large Stokes shift (130 nm) and a short response time (30 min), and it is highly selective and sensitive (~160-fold) in the detection of thiophenols, with marked fluorescence in the presence of thiophenols. probe-KCP responds to thiophenols with a good range of linearity (0⁻15 µM) and a detection limit of 28 nM (R² = 0.9946) over other tested species mentioned including aliphatic thiols, thiophenol analogues, common anions, and metal ions. The potential applications of this carbazole-chalcone fluorescent probe was successfully used to determine of thiophenols in real water samples and living cells with good performance and low cytotoxicity. Therefore, this probe has great potential application in environment and biological samples.

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups.

Fluorine chemistry plays an increasingly important role in pharmaceutical, agricultural, and materials industries. The incorporation of fluorine-containing groups into organic molecules can improve their chemical and physical properties, which attracts continuous interest in organic synthesis. Among various reported methods, transition-metal-catalyzed fluorination/fluoroalkylation has emerged as a powerful method for the construction of these compounds. This review attempts to describe the major advances in the transition-metal-catalyzed incorporation of fluorine, trifluoromethyl, difluoromethyl, trifluoromethylthio, and trifluoromethoxy groups reported between 2011 and 2019.

Bromophenol curcumin analog BCA-5 exerts an antiangiogenic effect through the HIF-1α/VEGF/Akt signaling pathway in human umbilical vein endothelial cells.

The bromophenol curcumin analog 1,5-bis(3-bromo-4, 5-dimethoxyphenyl) penta-1, 4-dien-3-one (BCA-5) was assayed for antiangiogenic activity. Tandem mass tag labeling and liquid chromatography-tandem mass spectrometry were used to quantify the dynamic changes in the human umbilical vein endothelial cell (HUVEC) proteome. Functional annotation showed that BCA-5 might inhibit compounds related to the extracellular matrix, compounds that possess cytoskeletal protein-binding activity, and compounds that interact with cell motility-related enzymes, indicating antiangiogenic potential. In-vitro experiments have shown that BCA-5 inhibited HUVEC proliferation and induced HUVEC apoptosis. BCA-5 inhibited HUVEC migration, invasion, and tubular formation. BCA-5 decreased the phosphorylation of Akt and endothelial nitric oxide synthase; it also reduced the expression of hypoxia-inducible factor-1α and vascular endothelial cell growth factor in a dose-dependent manner. These results suggest that BCA-5 has antiangiogenic properties and should be considered a potent antiangiogenesis drug for the treatment of cancer.

Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors.

A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47 nM, 188.7 nM and 65.36 nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.

A Novel Bromophenol Derivative BOS-102 Induces Cell Cycle Arrest and Apoptosis in Human A549 Lung Cancer Cells via ROS-Mediated PI3K/Akt and the MAPK Signaling Pathway.

Bromophenol is a type of natural marine product. It has excellent biological activities, especially anticancer activities. In our study of searching for potent anticancer drugs, a novel bromophenol derivative containing indolin-2-one moiety, 3-(4-(3-([1,4'-bipiperidin]-1'-yl)propoxy)-3-bromo-5-methoxybenzylidene)-N-(4-bromophenyl)-2-oxoindoline-5-sulfonamide (BOS-102) was synthesized, which showed excellent anticancer activities on human lung cancer cell lines. A study of the mechanisms indicated that BOS-102 could significantly block cell proliferation in human A549 lung cancer cells and effectively induce G0/G1 cell cycle arrest via targeting cyclin D1 and cyclin-dependent kinase 4 (CDK4). BOS-102 could also induce apoptosis, including activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP, ΔΨm), and leading cytochrome c release from mitochondria. Further research revealed that BOS-102 deactivated the PI3K/Akt pathway and activated the mitogen-activated protein kinase (MAPK) signaling pathway resulting in apoptosis and cell cycle arrest, which indicated that BOS-102 has the potential to develop into an anticancer drug.