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201.
Dr. Xue-Yan Yang Dr. Hong-Yi Zhao Dr. Hao Lei Bo Yuan Prof. Shuai Mao Prof. Minghang Xin Prof. San-Qi Zhang 《ChemMedChem》2021,16(6):1000-1010
Despite remarkable clinical achievements, camptothecin (CPT) still suffers from poor solubility and severe toxicity. Therefore, it is necessary to redevelop CPT derivatives as supplementary antitumor agents with good water solubility and small side effects. In this work, 27 camptothecin derivatives were synthesized and screened for their cytotoxicity against A549 (lung) and HCT-116 (colon) cancer cell lines. Among them, compound B7 , 7-ethyl-10-(2-oxo-2-(4-methylpiperidin-1-yl)ethoxy)camptothecin,was demonstrated in vitro to be a more potent antitumor agent than SN-38 by comparison of their inhibitory activities against cell proliferation and colony formation and interference effect on process of cell cycle and cell apoptosis. Additionally, a molecular docking model revealed that B7 can interact with the topoisomerase I–DNA complex, and that the solubility of B7 reached 5.73 μg/mL in water. Moreover, B7 significantly inhibited tumor growth in an A549 xenograft model at dosages of 0.4 and 2.0 mg/kg, and exhibited minimum lethal doses comparable to those of irinotecan. These results indicated that B7 , with improved solubility, enhanced activity and acceptable acute toxicity, can be used as a lead compound for the development of novel anticancer agents. 相似文献
202.
Monika Absolonová Lucie Melounková Dr. Jaromír Vinklárek Dr. Jan Honzíček Libor Dostál Dr. Ondřej Mrózek 《ChemMedChem》2021,16(11):1805-1813
Cytotoxic complexes containing molybdenum are widely studied as a potential substitution for commercially used drugs that often suffer from pronounced side effects and cellular resistance. Compounds of the type [(η5-Cp′)Mo(CO)2(N,NL)][BF4], where Cp is cyclopentadienyl and N,NL is a bidentate ligand, are well known for their strong anticancer activity. It is a generally accepted paradigm that the nature of the coordinated N,NL ligand has a major impact on the cytotoxicity. In this study, a series of new functionalised Cp complexes of molybdenum was synthesised from derivatised fulvenes as π-ligand precursors. Indeed, the coordination sphere‘s modulation by various N,N-chelating ligands afforded species active toward leukemic cell line MOLT-4 with IC50 values depending on the character of the N,N-chelator used. However, following study clearly showed that functionalisation of the Cp ring with an amine moiety considerably improved cytotoxicity. These results are of crucial importance for the future design of highly active cytotoxic drugs, as modification of cyclopentadienyl is believed to have a minor effect on biological activity. 相似文献
203.
Chang-Youh Tsai Song-Chou Hsieh Chih-Wei Liu Cheng-Shiun Lu Cheng-Han Wu Hsien-Tzung Liao Ming-Han Chen Ko-Jen Li Chieh-Yu Shen Yu-Min Kuo Chia-Li Yu 《International journal of molecular sciences》2021,22(6)
Polymorphonuclear neutrophils (PMNs) are traditionally regarded as professional phagocytic and acute inflammatory cells that engulf the microbial pathogens. However, accumulating data have suggested that PMNs are multi-potential cells exhibiting many important biological functions in addition to phagocytosis. These newly found novel activities of PMN include production of different kinds of cytokines/chemokines/growth factors, release of neutrophil extracellular traps (NET)/ectosomes/exosomes and trogocytosis (membrane exchange) with neighboring cells for modulating innate, and adaptive immune responses. Besides, PMNs exhibit potential heterogeneity and plasticity in involving antibody-dependent cellular cytotoxicity (ADCC), cancer immunity, autoimmunity, inflammatory rheumatic diseases, and cardiovascular diseases. Interestingly, PMNs may also play a role in ameliorating inflammatory reaction and wound healing by a subset of PMN myeloid-derived suppressor cells (PMN-MDSC). Furthermore, PMNs can interact with other non-immune cells including platelets, epithelial and endothelial cells to link hemostasis, mucosal inflammation, and atherogenesis. The release of low-density granulocytes (LDG) from bone marrow initiates systemic autoimmune reaction in systemic lupus erythematosus (SLE). In clinical application, identification of certain PMN phenotypes may become prognostic factors for severe traumatic patients. In the present review, we will discuss these newly discovered biological and pathobiological functions of the PMNs. 相似文献
204.
Gulderen Karakus Zubeyde Akin Polat Ali Fazil Yenidunya Haci Bayram Zengin Can Bulent Karakus 《Polymer International》2013,62(3):492-500
Poly[(maleic anhydride)‐co‐(vinyl acetate)] (MAVA) copolymer was synthesized by free radical polymerization reaction, in methyl ethyl ketone at 80 °C, using benzoyl peroxide as the initiator. The copolymer was then modified with a biomolecule, noradrenaline (NA). The modification reaction was performed at 70 °C in dimethylformamide containing triethylamine as the catalyst. The modified polymer was named MAVA/NA. Structural characterization of the copolymer and the modified product was carried out by Fourier transform infrared (FTIR) and 1H NMR and 13C NMR spectroscopy. The FTIR, 1H NMR and 13C NMR spectra confirmed that NA was successfully covalently bound to the MAVA copolymer backbone. Surface morphology was visualized by atomic force microscopy. The cumulative release of NA from MAVA/NA was determined in phosphate buffered saline solution for 7 days at 37 °C and compared with MAVA. Cytotoxicity of the MAVA/NA was evaluated by using a mouse fibroblast cell line (L929). Results obtained indicated that MAVA/NA had almost no toxicity and no negative effect on cell viability at 250 µg mL?1 concentration. © 2012 Society of Chemical Industry 相似文献
205.
Matthew Flegal Melinda Blimkie Sandrine Roch-Lefevre Eric Gregoire Dmitry Klokov 《International journal of molecular sciences》2013,14(12):23791-23800
Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO) at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation. 相似文献
206.
The effects of molecular weight (MW) and the degree of deacetylation (DD) of chitosan (CS) on the physicochemical properties, antibacterial activity, and cytotoxicity of CS/2‐glycerophosphate (GP)/nanosilver hydrogel in the development of a thermosensitive in situ formed wound dressing are examined herein. The gelation temperatures for the hydrogels were measured in the range of 32–37°C by manipulating the MW and DD of CS and the GP concentration. The structure of 88% DD CS hydrogel was more porous, uniform, and connective than that of the 80% DD CS hydrogel. The superior water vapor transmission rates of hydrogels with 80% and 88% DD CS were 7150 ± 52 and 9044 ± 221 gm?2 d?1, respectively. The skin permeations of nanosilver by the 80% and 88% DD CS hydrogels were 3.82 and 4.99 μg cm?2, respectively, in 24 h tests. Both the hydrogels with 6 and 12 ppm nanosilver showed cytotoxicity for HS68 cells. The diameters of the hydrogel's inhibition zones for Pseudomonas aeruginosa and Staphylococcus aureus increased when the concentration of nanosilver increased and the MW of the CS decreased. Therefore, the hydrogel could be prepared with lower MW CS and lower concentration of nanosilver in order to reduce the cytotoxicity of nanosilver, while maintaining similar antibacterial activity for a hydrogel prepared with higher concentration nanosilver and higher MW CS. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 相似文献
207.
Wei‐Lu Zhang Da‐Wei Yong Jin Huang Jia‐Hui Yu Shi‐Yuan Liu Ming‐Xia Fan 《应用聚合物科学杂志》2011,120(5):2596-2605
Methoxy poly (ethylene glycol)‐graft‐α, β‐poly (aspartic acid) derivatives (mPEG‐g‐PAA‐N3) were synthesized by sequential ring‐opening reaction of polysuccinimide (PSI) with mPEG‐NH2 (MW: 2000 Da), and 1‐azido‐3‐aminopropane, respectively. Then N2‐(hex‐5‐yne)‐diethylenetriamine‐tetra‐t‐butylacetate (DTTA‐der) was conjugated to mPEG‐g‐PAA‐N3 by click cycloaddition. After deprotection of carboxylic groups, mPEG‐g‐PAA‐DTTA macromolecular ligands were obtained. MPEG‐g‐PAA‐(DTTA‐Gd) complex nanomicelles were fabricated from mPEG‐g‐PAA‐DTTA and Gadolinium chloride. The formation of nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with core‐shell structures and narrow size distributions. Their sizes ranged from 50 to 80 nm, suggesting their passive targeting potential to tumor tissue. With the increase of graft degree (GD) of mPEG, the sizes of mPEG‐g‐PAA‐(DTTA‐Gd) nanomicelles showed a tendency to decrease. Compared with gadopentetate dimeglumine (Gd‐DTPA), mPEG‐g‐PAA‐(DTTA‐Gd) nanomicelles showed essential decreased cytotoxicity to KB cell line and enhanced T1‐weighted signal intensity, especially at low concentration of gadolinium (III), suggesting their great potentials as magnetic resonance imaging contrast agents. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 相似文献
208.
Shi-Yie Cheng Shang-Kwei Wang Mu-Keng Hsieh Chang-Yih Duh 《International journal of molecular sciences》2015,16(3):6140-6152
Five new polyoxygenated cembranoids, named (+)-1,15-epoxy-2-methoxy-12-methoxycarbonyl-11E-sarcophytoxide (1), (+)-2-epi-12-methoxycarbonyl-11E-sarcophine (2), 3,4-epoxyehrenberoxide A (3), ehrenbergol D (4) and ehrenbergol E (5), were obtained from the soft coral Sarcophyton ehrenbergi. The structures of 1–5 were established on the basis of comprehensive NMR and HR-ESI-MS analyses and by comparison with reported data in the literature. Compounds 4 and 5 showed moderate cytotoxicity against P-388 (mouse lymphocytic leukemia) cancer cell line with EC50 values of 2.0 and 3.0 μM, respectively. Compound 2 exhibited slight antiviral activity against HCMV (human cytomegalovirus) with IC50 values of 25.0 μg/mL. 相似文献
209.
Daniel Gromadzki Virginia Tzankova Magdalena Kondeva Cvetelina Gorinova Piotr Rychter Marcin Libera 《国际聚合物材料杂志》2017,66(18):915-925
Multifunctional nanocarriers are gaining increasing research interest as polymeric platforms for targeted drug delivery in cancer therapy and diagnosis. In this work, preparation and characterization of surfactant-free polyester nanoparticles (NPs) from a bio-based poly(butylene sebacate-co-butylene dilinoleate)s, poly(butylene sebacate) (PBSE)/poly(butylene dilinoleate) (PBDL), using nanoprecipitation, is reported. The polymeric nanoparticles (sizes narrowly distributed in a range less than 100?nm) were loaded with curcumin (CURC) with an encapsulation efficiency of 98% and drug loading (DL) content of 5–10% wtdrug/wtpolymer. The CURC-loaded nanoparticles were efficiently coated with a novel poly(sulfobetaine)-type zwitterionic polymer synthesized by nitroxide-mediated polymerization and postpolymerization functionalization step. Free and CURC formulated into noncoated and poly(sulfobetaine)-type zwitterionic polymer-coated nanoparticles were further investigated for cytotoxicity and antioxidant activity in a panel of human cell lines and rat liver microsomes, respectively. Formulated into coated NPs, CURC has superior cytotoxic and antioxidant activity versus the free drug and CURC incorporated in noncoated NPs. In addition, cell viability experiments of nonloaded nanoparticles, both coated and noncoated, demonstrated that developed nanoparticles are nontoxic, making them potentially suitable candidates for systemic passive targeting in cancer therapy, namely for treatment of solid tumors exhibiting high tumor accumulation of NPs due to enhanced permeability and retention effect. Polyzwitterion-coated nanoparticles exhibited slower drug release compared with the noncoated ones (half as much after 24?h) presumably due to the presence of the polymer shell around nanoparticles associated with a wider diffusion layer around the particles. 相似文献
210.
Gregg Caldwell Eberhard W. Neuse Constance E. J. van Rensburg 《Journal of Inorganic and Organometallic Polymers》1997,7(4):217-231
Several polymer-platinum conjugates comprising the square-planar cis-diaminedichloroplatinum(II) complex system of cisplatin-type anticancer drugs are screened for antiproliferative activity in cell culture tests. The water-soluble conjugates prepared in this study or taken from preceding investigations are obtained by platination of aliphatic polyamide carriers containing ethylenediamine segments as side-group or main-chain components. These segments, coordinating to the metal as cis-diamine chelating ligands, are bound to, or into, the carrier backbone through biofissionable amide links permitting drug release from the carrier. In vitro tests are performed against a HeLa human cervix carcinoma cell line. IC50 data, expressed as the concentration of Pt in the conjugates (g/ml), causing 50% inhibition of cell growth, show the highest activity, with IC50=14 g/ml, to be associated with a conjugate derived from a polyaspartamide carrier that contains the platinum complex as a side group in proximity to the main chain and, additionally, contains dimethylaminopropyl side groups as solubilizing functions. At the low end of the performance spectrum is a conjugate, with IC50>120 g/ml, possessing a similar backbone and metal-binding structure, yet comprising long poly(ethylene oxide) grafts. The latter apparently shield the complex-binding tether from enzymatic attack and thus prevent efficient intracellular release of the monomeric complex. Selected conjugates will be submitted for toxicological evaluation. 相似文献