Temporal changes in net ecosystem CO2 exchange and influential factors in an apple orchard in Northeast China.

The apple orchards in Liaoning, one of the four major apple-producing areas in Bohai Bay, Northeast China, play a crucial role in regulating the carbon sink effect. However, there is limited information on the variation in carbon flux and its influential factors in apple orchards in this region. To address this, CO2 flux data were monitored throughout the entire apple growth seasons from April to November in 2017 and 2018 in the apple (Malus pumila Mill. cv Hanfu) orchard in Shenyang, China. The energy closure of the apple orchard was calculated, and variations in net ecosystem exchange (NEE) at different time scales and its response to environmental factors were analyzed. Our results showed that the energy balance ratio of the apple was 0.74 in 2017 and 1.38 in 2018. NEE was generally positive in April and November and negative from May to October, indicating a strong carbon sink throughout the growth season. The daily average NEE ranged from - 0.103 to 0.094 mg m-2 s-1 in 2017 and from - 0.134 to 0.059 mg m-2 s-1 in 2018, with the lowest values observed in June and July. NEE was negatively correlated with net radiation, atmospheric temperature, saturated vapor pressure deficit, and soil temperature. These findings provide valuable insights for predicting carbon flux in orchard ecosystems within the context of global climate change.

Strategies to Promote the Journey of Nanoparticles Against Biofilm-Associated Infections.

Biofilm-associated infections are one of the most challenging healthcare threats for humans, accounting for 80% of bacterial infections, leading to persistent and chronic infections. The conventional antibiotics still face their dilemma of poor therapeutic effects due to the high tolerance and resistance led by bacterial biofilm barriers. Nanotechnology-based antimicrobials, nanoparticles (NPs), are paid attention extensively and considered as promising alternative. This review focuses on the whole journey of NPs against biofilm-associated infections, and to clarify it clearly, the journey is divided into four processes in sequence as 1) Targeting biofilms, 2) Penetrating biofilm barrier, 3) Attaching to bacterial cells, and 4) Translocating through bacterial cell envelope. Through outlining the compositions and properties of biofilms and bacteria cells, recent advances and present the strategies of each process are comprehensively discussed to combat biofilm-associated infections, as well as the combined strategies against these infections with drug resistance, aiming to guide the rational design and facilitate wide application of NPs in biofilm-associated infections.

Lipid-like gemcitabine diester-loaded liposomes for improved chemotherapy of pancreatic cancer.

Gemcitabine (GEM) is a non-selective chemotherapeutic agent used in the treatment of pancreatic cancer. Its antitumor efficacy is limited by a short plasma half-life and severe adverse reactions. To overcome these shortcomings, four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes. Through optimization, dimyristoyl GEM (dmGEM)-loaded liposomes (LipodmGEM) were successfully obtained with an almost complete encapsulation efficiency. Compared to free GEM, LipodmGEM showed enhanced cellular uptake and cell apoptosis, improved inhibition of cell migration on AsPC-1 cells and a greatly extended half-life (7.22 vs. 1.78 h). LipodmGEM succeeded in enriching the drug in the tumor (5.28 vs. 0.03 µmol/g at 8 h), overcoming a major shortcoming of GEM, showed excellent anticancer efficacy in vivo and negligible systemic toxicity, superior to GEM. Attractive as well, suspensions of LipodmGEM remained stable at 2-10 °C away from light for no <2 years. Our results suggest that LipodmGEM might become of high interest for treating pancreatic cancer while the simple strategy we reported might be explored as well for converting other antitumor drugs with high water-solubility and short plasma half-life into attractive nanomedicines.

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication.

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

Enhanced binding of ß-catenin and ß-TrCP mediates LMPt's anti-CSCs activity in colorectal cancer.

Cancer stem cells (CSCs), a subpopulation of tumor cells with the features of self-renewal, tumor initiation, and insensitivity to common physical and chemical agents, are the key to cancer relapses, metastasis, and resistance. Accessible CSCs inhibitory strategies are primarily based on small molecule drugs, yet toxicity limits their application. Here, we report a liposome loaded with low toxicity and high effectiveness of miriplatin, lipo-miriplatin (LMPt) with high miriplatin loading, and robust stability, exhibiting a superior inhibitory effect on CSCs and non-CSCs. LMPt predominantly inhibits the survival of oxaliplatin-resistant (OXA-resistant) cells composed of CSCs. Furthermore, LMPt directly blocks stemness features of self-renewal, tumor initiation, unlimited proliferation, metastasis, and insensitivity. In mechanistic exploration, RNA sequencing (RNA-seq) revealed that LMPt downregulates the levels of pro-stemness proteins and that the ß-catenin-mediated stemness pathway is enriched. Further research shows that either in adherent cells or 3D-spheres, the ß-catenin-OCT4/NANOG axis, the vital pathway to maintain stemness, is depressed by LMPt. The consecutive activation of the ß-catenin pathway induced by mutant ß-catenin (S33Y) and OCT4/NANOG overexpression restores LMPt's anti-CSCs effect, elucidating the key role of the ß-catenin-OCT4/NANOG axis. Further studies revealed that the strengthened binding of ß-catenin and ß-TrCP initiates ubiquitination and degradation of ß-catenin induced by LMPt. In addition, the ApcMin/+ transgenic mouse model, in which colon tumors are spontaneously formed, demonstrates LMPt's potent anti-non-CSCs activity in vivo.

Novel 5-Fluorouracil Carbonate-Loaded Liposome: Preparation, In Vitro, and In Vivo Evaluation as an Antitumor Agent.

5-Fluorouracil (5-FU) is a chemotherapeutic drug against many types of cancers, especially colorectal cancer. However, its short plasma half-life and serious adverse reactions limit its wide clinical applications. To overcome these shortcomings, a novel lipophilic 5-FU carbonate [XL-01, (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) methyl tetradecyl carbonate] was designed, synthesized, and encapsulated into liposome (LipoXL-01) by a thin-film dispersion method through formulation screening and optimization. LipoXL-01 was characterized by a particle size of around 100 nm, polydispersity index of 0.200, ζ-potential value of -41 mV, encapsulation efficiency of 93.9%, and drug-loading efficiency of 11.6%. The cellular uptake of LipoXL-01 was increased in a concentration-dependent manner on HCT15 cells. LipoXL-01 could enhance the induction of cell apoptosis and the inhibition of cell migration and arrest the ability of the cell cycle at the S-phase on HCT15 cells better than 5-FU. Additionally, LipoXL-01 exhibited a slow drug release profile with a cumulative release rate of 12% in 8 h. The results of pharmacokinetic and biodistribution studies revealed that LipoXL-01 had a long plasma half-life (7.21 h) and a high tumor accumulation (733 nmol/g at 8 h). The in vivo antitumor effect study also showed that LipoXL-01 had more potent efficacy than 5-FU (65 vs 48% of the tumor-inhibition rate). Simultaneously, negligible systemic toxicity was observed via analyzing the body weight as well as hematological and pathological parameters in the tested mice. The current study suggested that LipoXL-01 might be a promising nanocandidate for chemotherapy of colorectal cancer.

Mulched drip irrigation and biochar application reduce gaseous nitrogen emissions, but increase nitrogen uptake and peanut yield.

Nitrous oxide and ammonia emissions from farmland need to be abated as they directly or indirectly affect climate warming and crop yield. We conducted a two-year field experiment to investigate the effect of biochar applied at two rates (no biochar application vs. biochar applied at 10 t ha-1) on gaseous nitrogen (N) losses (N2O emissions and NH3 volatilization), plant N uptake, residual soil mineral N, and peanut (Arachis hypogaea L.) yield under three irrigation regimes: furrow irrigation (FI), drip irrigation (DI), and mulched drip irrigation (MDI). We found that MDI reduced residual (post-harvest) soil mineral N, cumulative N2O emissions, and yield-scaled N2O emissions as compared to FI. Biochar application increased residual soil NO3--N and decreased yield-scaled N2O emissions as compared with the control without biochar application. Under the three irrigation regimes, biochar application decreased cumulative NH3 volatilization and increased plant N uptake and yield compared with the control. Biochar application improved the sustainability of peanut production and could be used to alleviate the environmental damage associated with gaseous N emissions. Where possible, biochar application under MDI in peanut fields is recommended as a management strategy to minimize gaseous N losses.

Design, synthesis and biological evaluation of nitrofuran-1,3,4-oxadiazole hybrids as new antitubercular agents.

Three series of novel nitrofuran-1,3,4-oxadiazole hybrids were designed and synthesized as new anti-TB agents. The structure activity relationship study indicated that the linkers and the substituents on the oxadiazole moiety greatly influence the activity, and the substituted benzenes are more favoured than the cycloalkyl or heterocyclic groups. Besides, the optimal compound in series 2 was active against both MTB H37Rv strain and MDR-MTB 16883 clinical isolate and also displayed low cytotoxicity, low inhibition of hERG and good oral PK, indicating its promising potential to be a lead for further structural modifications.

Promoted antitumor therapy on pancreatic cancer by a novel recombinant human albumin-bound miriplatin nanoparticle.

Pancreatic cancer is an aggressive and highly lethal disease with a very poor prognosis. Our previous study found miriplatin can inhibit proliferation of various tumor cells, including pancreatic cancer cells. For the chemotherapy of pancreatic cancer, a novel recombinant human serum albumin (rHSA)-bound miriplatin nanoparticles (rHSA-miPt) were constructed by emulsion-diffusion evaporation method. The optimal formulation was composed of 150 mg of rHSA and 30 mg of miriplatin. The key parameters in rHSA-miPt production were 10 min of high-pressure homogenization in a solution with volume ratio of 10:2 of 5% glucose and chloroform. The rHSA-miPt was characterized with a particle size of 61 ± 10 nm, a zeta potential value of -18 ± 5 mV, encapsulation efficiency of 98.4%, drug loading of 16.4%, T1/2 of 13.3 h and Vd of 0.5 L in Sprague Dawley rats. The concentrations of platinum (Pt) in the tumors were 15 and 22-fold higher than those in the blood at 24 and 72 h in tumor-bearing mice, respectively. The internalization of rHSA-miPt through caveolae-dependent pathway. In vitro, the half-maximal inhibitory concentration (IC50) of rHSA-miPt was 12.7 µM vs more than 100 µM of gemcitabine (Gem). The inhibition rate of tumor growth was 76% of rHSA-miPt and 51% of Gem, respectively. Compared with Gem, rHSA-miPt was identified to be safer and less toxic based on body weight loss in mice (0% vs 20%), the survival rate of mice (100% vs 80%) and hematological and biochemical parameters of the mice including leukocytes, lymphocytes, neutrophils, monocytes, serum alanine aminotransferase and aspartate aminotransferase. The present study revealed that rHSA-miPt might be a promising candidate for pancreatic cancer therapy.

Photosynthesis, Chlorophyll Fluorescence, and Yield of Peanut in Response to Biochar Application.

The effect of biochar application on photosynthetic traits and yield in peanut (Arachis hypogaea L.) is not well understood. A 2-year field experiment was conducted in Northwest Liaoning, China to evaluate the effect of biochar application [0, 10, 20, and 40 t ha-1 (B0, B10, B20, and B40)] on leaf gas exchange parameters, chlorophyll fluorescence parameters, and yield of peanut. B10 improved photochemical quenching at flowering and pod set and reduced non-photochemical quenching at pod set, relative to B0. B10 and B20 increased actual photochemical efficiency and decreased regulated energy dissipated at pod set, relative to B0. B10 significantly increased net photosynthetic rate, transpiration rate, stomatal conductance, and water use efficiency at flowering and pod set, relative to B0. Compared with B0, B10 significantly improved peanut yield (14.6 and 13.7%) and kernel yield (20.2 and 14.4%). Biochar application increased leaf nitrogen content. B10 and B20 significantly increased plant nitrogen accumulation, as compared to B0. The net photosynthetic rate of peanut leaves had a linear correlation with plant nitrogen accumulation and peanut yield. The application of 10 t ha-1 biochar produced the highest peanut yield by enhancing leaf photosynthetic capacity, and is thus a promising strategy for peanut production in Northwest Liaoning, China.

Design, synthesis and biological activity of N-(amino)piperazine-containing benzothiazinones against Mycobacterium tuberculosis.

A series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in our lab, were designed and synthesized as new anti-TB agents. Many of the compounds exhibited excellent in vitro activity against both drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates (MIC: < 0.016 µg/mL), and good safety index (CC50: >64 µg/mL). Especially compound 1o displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its promising potential to be a lead compound for future antitubercular drug discovery.

Antisense microRNA185 loaded liposome for efficient inhibition of the hepatic endogenous microRNA185 level.

MicroRNA185 (miR185), an endogenous noncoding RNA with 23 nucleotides, is one of key posttranscriptional modulators of cholesterol metabolism in hepatic cells. The antisense inhibitor of miR185 (miR185i) could decrease cholesterol level in vivo, providing a promising agent for anti-atherosclerosis strategy. In this work, a novel LipomiR185i was constructed by thin film hydration method and post-PEGylation as DOPE: DOTAP: Chol: DSPE-PEG2000 at the molar ratio of 1:1:1:0.1 with a nitrogen-to-phosphate ratio of 3, through the optimization of three cationic lipids (DOTAP, DODMA and DLin-MC3-DMA), six helper lipids (PC-98T, HSPC, DOPE, DMPC, DPPC and DSPC), different amounts and incorporation approaches of DSPE-PEG2000 and nitrogen-to-phosphate ratio. LipomiR185i was characterized with a particle size of 174 ± 11 nm, a zeta potential of 7.0 ± 3.3 mV, high encapsulation efficiency and transfection activity. It could protect miR185i from the rapid degradation by nucleases in serum, enhance cellular uptake and promote lysosomal escape in HepG2 cells. LipomiR185i could accumulate in the liver and remain for at least two weeks. More importantly, LipomiR185i significantly down-regulated the hepatic endogenous miR185 level in vitro and in vivo without significant tissue damage at 14 mg⋅kg-1. The construction of LipomiR185i provides a potential anti-atherosclerotic nanodrug as well as a platform for delivering small RNAs to the liver efficiently and safely.

Evaluation of antitumor efficacy of folate-poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine based liposome.

This study aims to explore and evaluate the antitumor efficacy of doxorubicin (DOX)-loaded liposomes containing the novel tri-block polymer folate-poly (2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (F-PEOz-DSPE), compared with folate-polyethylene glycol-distearoyl phosphatidyl ethanolamine (F-PEG-DSPE) to offer an alternative for PEG decorated carriers. PEOz, a pH-sensitive polymer, exhibits similar solubility and segmental flexibility to PEG. In our previous study, PEOz was employed to an F-PEOz-DSPE which was segmentally similar to F-PEG-DSPE and exhibited selective targeting and pH-sensitivity in tumor cells. In this work, DOX-loaded liposomes containing F-PEOz-DSPE (F-PEOz liposome) or F-PEG-DSPE (F-PEG liposome) were prepared. In vivo/vitro antitumor efficacy and biodistribution were compared between the two liposomes. F-PEOz liposome showed higher in vitro antitumor activity and significantly stronger inhibition of tumor growth in HeLa tumor-bearing nude mice (tumor inhibition rate, 81.20 vs 52.99% with the treatment of 9 mg/kg DOX-loaded F-PEOz liposome/F-PEG liposome) and much less toxicity than free DOX. In vivo fluorescence imaging experiment confirmed that F-PEOz liposome accumulated much more than F-PEG liposome in tumor. Based on the above, F-PEOz liposome may be a promising carrier in tumor chemotherapy to achieve better therapeutic efficacy.

Endocytosis and Organelle Targeting of Nanomedicines in Cancer Therapy.

Nanomedicines (NMs) have played an increasing role in cancer therapy as carriers to efficiently deliver therapeutics into tumor cells. For this application, the uptake of NMs by tumor cells is usually a prerequisite to deliver the cargo to intracellular locations, which mainly relies on endocytosis. NMs can enter cells through a variety of endocytosis pathways. Different endocytosis pathways exhibit different intracellular trafficking routes and diverse subcellular localizations. Therefore, a comprehensive understanding of endocytosis mechanisms is necessary for increasing cellular entry efficiency and to trace the fate of NMs after internalization. This review focuses on endocytosis pathways of NMs in tumor cells, mainly including clathrin- and caveolae-mediated endocytosis pathways, involving effector molecules, expression difference of those molecules between normal and tumor cells, as well as the intracellular trafficking route of corresponding endocytosis vesicles. Then, the latest strategies for NMs to actively employ endocytosis are described, including improving tumor cellular uptake of NMs by receptor-mediated endocytosis, transporter-mediated endocytosis and enabling drug activity by changing intracellular routes. Finally, active targeting strategies towards intracellular organelles are also mentioned. This review will be helpful not only in explicating endocytosis and the trafficking process of NMs and elucidating anti-tumor mechanisms inside the cell but also in rendering new ideas for the design of highly efficacious and cancer-targeted NMs.

Design, synthesis and antimycobacterial activity of new benzothiazinones inspired by rifampicin/rifapentine.

A series of novel benzothiazinone derivatives containing a N-((methylene)amino)piperazine moiety, inspired by rifampicin/rifapentine, were designed and synthesized. Seven compounds 1a and 1e-j show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and drug-resistant clinical isolates (MIC: <0.029-0.110 µM), and accepted selective index (>1100->4000). Compound 1h displays good safety and pharmacokinetic profiles, suggesting its promising potential to be lead compound for future antitubercular drug discovery.

[Optimization of mulched drip irrigation amount for peanut based on AHC model in northwestern Liaoning, China]. / 基于AHC模型的辽西北花生膜下滴灌灌水量优化.

To evaluate the applicability of AHC (agro-hydrological chemical and crop systems simulator) model and explore the suitable irrigation amount for peanut (Arachis hypogaea) under mulched drip irrigation in the semi-arid areas of northwestern Liaoning Province, based on the two-year field experimental data of peanut in 2016 and 2017, the model parameters were firstly chosen for global sensitivity analysis. Then, module parameters of soil moisture and crop growth were calibrated and validated. Finally, AHC model was used to analyze the responses of peanut yield and water use efficiency (WUE) to different irrigation amounts. The results showed that the two extremely sensitive parameters of the model were saturated hydraulic conductivity in the first and second layers of soil. Root mean square error (RMSE) and mean relative error (MRE) between simulated and measured values of soil water content ranged from 0.02 to 0.03 cm3·cm-3 and 1.5% to 2.3%, respectively. The RMSE and MRE of leaf area index and plant height were 0.3-0.6, 4.2-4.5 cm, and 5.0%-8.9%, 5.2%-6.8%, respectively. The MRE of peanut yield and water consumption were both within 5%, indicating that the model was suitable for simulating soil moisture and peanut growth in the northwest Liaoning Province. With the increases of irrigation amounts, peanut yield increased and water use efficiency decreased. Considering both peanut yield and WUE, we recommend that the optimal mulched drip irrigation amounts for peanut in the semi-arid areas of Northwestern Liaoning in test year (normal year) was 80-97 mm.

The Endocytic Mechanism and Cytotoxicity of Boron-Containing Vesicles.

A novel polymer (PEG2000-carborane), self-assembling into spherical vesicles (boron-containing vesicles, BCVs), could be quickly taken up by tumor cells and had an enhance stability in the bloodstream in previous study. To have more comprehensive understanding of BCVs, endocytic mechanism and cytotoxicity assessment were conducted. The results showed that BCVs were taken up in the intact form with cholesterol-dependent pathway during endocytosis, and BCVs exhibited nearly no cytotoxicity. BCVs could accumulate within tumors for at least 24 h. The data would provide reference information and guidance for BCVs' multifunctional application serving as a boron delivery agent for boron neutron capture therapy (BNCT), a hydrophilic and/or hydrophobic drug carrier and a diagnostic imaging fluorescent probe.

Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.

Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.

Effect of a poloxamer 407-based thermosensitive gel on minimization of thermal injury to diaphragm during microwave ablation of the liver.

AIM: To assess the insulating effect of a poloxamer 407 (P407)-based gel during microwave ablation of liver adjacent to the diaphragm. METHODS: We prepared serial dilutions of P407, and 22.5% (w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits (gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS: In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups (P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups (P > 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum (all P > 0.05). CONCLUSION: Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted.

Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety.

A series of novel ATB-429 (an anti-inflammatory candidate) derivatives containing a nitric oxide (NO)-releasing moiety were designed, synthesized and evaluated for their in vitro activity against six human cancer cell lines. Our results reveal that phenylsulfonylfuroxan-based derivatives have considerable antitumor activity, and compounds 7-9 (IC50s: 0.256-3.024 µM) against HT-29 and PANC-1, 8a,b (IC50s: 2.677-3.051 µM) against MCF-7 and 8a (IC50: 1.270 µM) against DU145 are more active than Vandetanib (IC50s: 1.925-4.107 µM).