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1.
Nikolaos S. Soukos Michael R. Hamblin Tayyaba Hasan† 《Photochemistry and photobiology》1997,65(4):723-729
Abstract— The effect of charge on the cellular uptake, localization and phototoxicity of conjugates between chlorine6 ( c e6 ) and poly-L-lysine was studied in vitro. These conjugates (average MW35–55 kDa) were synthesized to have polycationic, polyanionic or neutral charges. Two human cell lines (A431 epidermoid carcinoma cells and EA.hy926 hybrid endothelial cells) were studied and the cellular uptake of c e6 delivered by the conjugates of varying charge and free c e6 was measured at conjugate c e6 equivalent concentrations up to 0.4 μM. Uptake was time and concentration dependent and temperature dependent in the case of neutral and anionic conjugates. Relative uptake at 6 h for A431 cells was 73:15:4:1 and for EA. hy926 cells was 63:11:3:1 for cationic, anionic, neutral and free c e6 , respectively, but EA. hy926 cells took up 1.5-2 times as much c e6 from all the conjugates as A431 cells. Localization as studied by fluorescence microscopy indicated that the cationic conjugate was in aggregates bound to the plasma membrane, while the other forms were internalized in organelles and membranes. Phototoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetra-zolium bromide (MTT) assay after irradiation with5–20 J cm−2 of 666 nm light. In contrast to the uptake, the order of phototoxicity for both cell types per mole of c e6 uptake per cell was neutral ≫ anionic > cationic > free c e6 . Polymeric c e6 conjugates bearing positive, negative and neutral charges may have different tissue-localizing properties and could play a role in photodynamic therapy. 相似文献
2.
A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety, which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-75 A549, H460 and HT29) and PD-1/PD-L1 inhibitory activities. Moreover, several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293). The most promising compound llo showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45, 8.65, 6,57 and 8.13 gmol/L, respectively, and displayed weak cytotoxicity on the normal cell(HEK-293). Furthermore, screening of PD-1 /PD-L1 inhibitory activity revealed that compound llo could effectively inhibit the binding of PD-1/PD-L1, and the binding interactions of compound llo with PD-L1 protein were explored by molecular docking. All above evidences showed that compound llo might be worthy of further study as a valuable leading compound for the treatment of cancer. 相似文献
3.
LIU Zijian HOU Yunlei ZHANG Guogang XU Ning MI Bin GONG Ping ZHAO Yanfang 《高等学校化学研究》2015,31(2):235-243
A series of novel indolin-2-one derivatives containing 4-thiazolidinone moiety(7a―7r) were synthesized and evaluated for their in vitro antitumour activities against MDA-MB-231(human breast cancer), H460(human lung cancer) and HT-29(human colon cancer) cell lines by standard 3-(4,5-dimethylthiazae-2-yl)-2,5-diphenyltetrazo- lium bromide(MTT) assay. Representative compounds(7d, 7k, 7m, 7p) with higher cytotoxicity were further examined against one normal cell line(WI-38, human fetal lung fibroblasts). The preliminary investigation shows that most of the compounds display moderate to excellent potency and high selectivity against different human cancer cell lines. In particular, the most potent compound 7m shows promising cytotoxicity against MDA-MB-231, H460 and HT-29 cell lines with IC50 values of 0.78, 0.056 and 0.018 μmol/L, respectively. The potency is much higher than that of Sunitinib(IC50=3.46 μmol/L against MDA-MB-231, IC50=2.59 μmol/L against H460, IC50=1.50 μmol/L against HT-29) by 4.4, 46.3 and 83.3 fold. 相似文献
4.
研究了结肠癌细胞CL-187、肺腺癌细胞L-973以及乳腺癌细胞MCF-7分别对99mTcN-MIBI和99mTc-MIBI配合物的摄取情况.结果表明,99mTcN-MIBI在3种肿瘤细胞内培养20~40min时的摄取达到极大值,并且摄取量明显高于99mTc-MIBI,特别是在结肠癌细胞CL-187中.99mTcN-MIBI在乳腺癌细胞MCF-7内的摄取量最高,培养40min时的单位细胞摄取百分率约为30%/105个细胞;在结肠癌细胞CL-187内的摄取量次之;在肺腺癌细胞L-973内的摄取量最低.细胞摄取条件实验结果表明:细胞浓度和培养温度的变化均会对细胞摄取产生影响. 相似文献
5.
A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively. 相似文献
6.
Lanthanide-doped upconversion nanoparticles(UCNPs) are great promising to apply to biomedical imaging and therapy. We prepared NaYF4:Yb3+,Er3+ nanoparticles with different surface ligands, i.e., without any ligands(bare), coordinated with 2-aminoethyl dihydrogen phosphate(AEP), polyacrylic acid(PAA) or polyallylamine (PAAm), via a simple two-step ligand exchange of oleic acid capped NaYF4:Yb3+,Er3+ nanoparticles. Although the surface modification retained the crystal structure and transimission electron microscope(TEM) size distribution of the nanoparticles, and good dispersibility in aqueous solution and did not significantly change the upconversion luminescence, distinct differences were observed in the surface charge and hydrodynamic diameter. The cellular uptake and cytotoxicity of the nanoparticles were studied on two different cell lines, breast cancer MCF-7 and fibroblast 3T3. Confocal microscopy images demonstrate that PAAm-coordinated UCNPs can enhance the cellular uptake and endocytosis, whereas AEP- and PAA-coordinated UCNPs show a very low level of nonspecific adsorption. Biocompatibility studies based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, however, indicate that PAAm-coordinated UCNPs are more toxic than the other two, and thus need further modifiaction(like PEG coordinating) to improve their biocompatibility. These results are important to the knowledge base required for the biomedical application of the UCNPs. 相似文献
7.
HUANG Qiang FU Qiangqiang LIU Yajing BAI Jinying WANG Qianying LIAO Huimin GONG Ping 《高等学校化学研究》2014,30(2):257-265
In an attempt to develop potent and selective anticancer agents,we designed and synthesized a series of novel bis(morpholino-1,3,5-triazine) derivatives beating aylmethylene hydrazine moiety and evaluated their cytotoxicity,in vitro,against H460(non-small-cell lung cancer),HT-29(human colorectal cancer) and MDA-MB-231(human breast cancer) cell lines.The pharmacological results indicate that all the compounds exhibit enhanced cytotoxicity than BMCL-200908069-1,and six target compounds(7e,7h,7j,9a,9b,9c) were superior to PAC-1 against all the tested cancer cell lines.The most active compound 7j,with IC50(inhibitory concentration 50%)values of 0.75,0.34 and 0.60 μ mol/L against HT-29,H460 and MDA-MB-231 cancer cell lines,was 39-,28-,and 60-fold more potent than BMCL-200908069-1 (29.24,9.52 and 36.21 μmol/L),respectively. 相似文献
8.
Ghadah F. ALJOHANI Fatma A. A. EL-HAG Mohamed S. BEKHEIT Ewies F. EWIES May A. EL-MANAWATY 《高等学校化学研究》2022,38(4):1073-1082
A library of novel spiro[pyrazole-4,5'-isoxazoline]-5-one derivatives were designed and synthesized using a concise and efficient one-pot reaction protocol through 1,3-dipolar cycloaddition between 4-benzylidene-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and chlorooximes. The synthesized derivatives were elucidated and characterized based on their spectroscopic data, including infrared spectrometry(IR), 1H NMR, 13C NMR, and elemental and mass spectral analysis. The synthesized compounds were evaluated for their antitumor inhibition potency against four human cancer cell lines, including human prostatic adenocarcinoma (PC3), human colorectal carcinoma(HCT116), human liver hepatocellular carcinoma(HepG2) and breast adenocarcinoma (MCF7). The outcomes were compared with the standard reference drug Doxorubicin. Among the synthesized chlorooximes, compounds 6d and 6e were the most active compounds on all cell lines. The spiro[pyrazole-4,5'-isoxazoline]-5-one derivatives 7a and 7c were active on the HepG2 liver cancer cell line. In comparison, compounds 7f and 7g were moderately active on the MCF7 cell line. The structure-activity relationship was explored for the synthesized compounds. Besides, in silico analysis of physicochemical, adsorption, distribution, metabolism, excretion and toxicity(ADMET) properties were done to determine the potential capacity of drug candidates. Molecular docking study onto the epidermal growth factor(EGF) tyrosine kinase receptor(3POZ) was done for the most active compounds to validate the reliability of in vitro anticancer screenings. 相似文献
9.
W Zhu X Zhai Q Fu F Guo M Bai J Wang H Wang P Gong 《Chemical & pharmaceutical bulletin》2012,60(8):1037-1045
Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003?μM, 0.42?μM and 0.74?μM, which was 1.6- to 290-fold more potent than GDC-0941. 相似文献
10.
Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells
Young Bin Hong Hyo Jin Kang Hee Jeong Kim Eliot M. Rosen Sivanesan Dakshanamurthy Riccardo Rondanin Riccardo Baruchello Giuseppina Grisolia Simoni Daniele Insoo Bae 《Experimental & molecular medicine》2009,41(3):151-160
Resveratrol has been reported to possess cancer preventive properties. In this study, we analyzed anti-tumor activity of a newly synthesized resveratrol analog, cis-3,4'',5-trimethoxy-3''-hydroxystilbene (hereafter called 11b) towards breast and pancreatic cancer cell lines. 11b treatments reduced the proliferation of human pancreatic and breast cancer cells, arrested cells in the G2/M phase, and increased the percentage of cells in the subG1/G0 fraction. The 11b treatments also increased the total levels of mitotic checkpoint proteins such as BubR1, Aurora B, Cyclin B, and phosphorylated histone H3. Mechanistically, 11b blocks microtubule polymerization in vitro and it disturbed microtubule networks in both pancreatic and breast cancer cell lines. Computational modeling of the 11b-tubulin interaction indicates that the dimethoxyphenyl group of 11b can bind to the colchicine binding site of tubulin. Our studies show that the 11b treatment effects occur at lower concentrations than similar effects associated with resveratrol treatments and that microtubules may be the primary target for the observed effects of 11b. These studies suggest that 11b should be further examined as a potentially potent clinical chemotherapeutic agent for treating pancreatic and breast cancer patients. 相似文献
11.
以3,4-二甲氧基苯甲醛与3,4-二甲氧基苯乙酸为起始原料,经Perkin缩合、自由基氧化偶联反应、Swern氧化、还原胺化及付克酰基化等7步反应全合成了娃儿藤碱类似物DCB-3501,其结构经1H NMR和ESI-MS确证。体外细胞毒性测试结果表明:DCB-3501对人结肠癌细胞HCT116、人胃癌细胞BGC-823、人肝癌细胞HepG-2、人宫颈癌细胞HeLa和人大细胞肺癌细胞H460的IC50分别为20.0 μmol·L-1, 50.9 μmol·L-1, 2.1 μmol·L-1, 65.8 μmol·L-1和30.8 μmol·L-1。 相似文献
12.
Aye Aye Mar Ali Koohang Nathan D. Majewski Erika L. Szotek David A. Eiznhamer Michael T. Flavin Ze Qi Xu 《中国化学快报》2009,20(10):1141-1144
28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2-hydroxyethyl iodide followed by oxidation and reduction.Direct reaction of betulin (5) or betulone (10) with ethyl bromoacetate led to 28-O-acylation, instead of 28-O-alkylation.The targeted compounds 3 and 4 were not cytotoxic at the highest concentrationtested (75 mmol/L), suggesting that elongation of the chain length at the 28-position in both betulinic acid (1) and betulonic acid (2)was detrimental to the cytotoxicity.The acylation products 28-O-bromoacetates (8a, 8b and 11) and 28-O-methoxyacetate 13exhibited cytotoxicity against several cancer cell lines tested. 相似文献
13.
Brasseur N Ménard I Forget A el Jastimi R Hamel R Molfino NA van Lier JE 《Photochemistry and photobiology》2000,72(6):780-787
High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1-2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5-10 microM dye followed by a 90 min washout period and a light dose of 5-10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 x 10(6) cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. 相似文献
14.
Scott L. Gibson Marwan K. Al-Shawi Alan E. Senior Russell Hilf 《Photochemistry and photobiology》1995,61(4):390-396
Abstract— The effectiveness of photodynamic therapy against P-glycoprotein ATPase activity in multidrug-resistant cells was studied. Chinese hamster ovary AUXB1 (drug-sensitive) and CR1R12 (multidrug-resistant) cell lines were compared with respect to uptake of 14 C-polyhematoporphyrin and porphyrin photosensitization. Phototoxicity of Photofrin® was similar in both cell lines, and no major differences in uptake or efflux of 14 C-polyhematoporphyrin were observed. Porphyrin photosensitization in vitro of CR1R12 cells or isolated plasma membranes from these cells caused inhibition of P-glycoprotein ATPase activity. Application of porphyrin photosensitization at a sublethal level to CR1R12 cells resulted in a small but significant increase in adriamycin-induced cytotoxicity. The hydrophobic "picket-fence" porphyrin, meso -tetrakis-( o -propionamidophenyl)porphyrin,α,α,α,β-isomer, was more inhibitory toward P-glycoprotein ATPase activity than the two less hydrophobic porphyrins tetraphenylporphine tetrasulfonate and Photofrin®. 相似文献
15.
Makito Miyake Masazumi Ishii Kiyotaka Kawashima Tetsuro Kodama Kokichi Sugano Kiyohide Fujimoto Yoshihiko Hirao 《Photochemistry and photobiology》2009,85(4):1020-1027
Photodynamic therapy mediated by 5-aminolevulinic acid (ALA-PDT) has been developed as a therapeutic modality for refractory superficial bladder cancers. Here, in experiments using urothelial cancer cell lines, we investigated the effects of siRNA modulating heme-synthetic and degradation pathways for ALA-PDT. Targeted knockdown of ferrochelatase (FECH) suppressed heme synthesis and significantly increased intracellular protoporphyrin IX (PpIX) accumulation, leading to enhanced phototoxicity in four of five cell lines. Heme oxygenase-1 (HO-1) is recognized as important for cytoprotection against oxidative stress such as PDT. Targeted knockdown of HO-1 leads to decreased intracellular PpIX accumulation, resulting in a failure to enhance ALA-PDT effect in four cell lines. Knockdown of HO-1 caused marked growth inhibition in UM-UC-2 overexpressing HO-1, whereas no inhibitory effect was observed in UM-UC-3 lacking HO-1 expression. Moreover, HO-1 protein levels and (GT) n repeat polymorphism of the HO-1 gene promoter region were examined with the implication that the constitutive expressions of HO-1 protein were associated with a shorter (GT) n repeat. Our results suggested that (1) FECH siRNA improved the phototoxicity of ALA-PDT, (2) overexpression of HO-1 was associated with shorter (GT) n repeat of the promoter region, and (3) siRNA-mediated knockdown of HO-1 could suppress the growth of bladder cancer cells overexpressing HO-1. 相似文献
16.
A series of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives was designed and synthesized.All of them were screened for their cytotoxic activities against large cell lung cancer(H460),colon cancer (HT-29) and adenocarcinomic lung cancer(A549) cell lines in vitro.The pharmacological results indicate that most of the target compounds show moderate to significant activities.Especially compound 17 exhibits the most potent antitumor activities against H460,HT-29 and A549 cell lines with IC50 values of 0.57,0.45 and 1.45 μmol/L,respectively. 相似文献
17.
In our screening for photosensitizers from natural resources, 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester (compound 1) was isolated for the first time from an Araceae plant. To evaluate the efficacy of compound 1 as a photosensitizer for head and neck cancers, compound 1 was studied in reference to a known photosensitizer pheophorbide-a (Pha), in terms of photophysical properties, singlet oxygen generation and in in vitro experiments (intracellular uptake and phototoxicity assays) in two oral (HSC2 and HSC3) and two nasopharyngeal (HK1 and C666-1) cancer cell lines. In this study, compound 1 exhibited higher intracellular uptake over 24 h compared with Pha in both HSC3 and HK1 cells. When activated by ≥4.8 J cm(-2) of light, compound 1 was slightly more potent as a photosensitizer than Pha by consistently having marginally lower IC(50) values across different cell lines. In flow cytometry experiments to study the mechanism of photoactivated cell death in HSC3, compound 1 was observed to induce more pronounced apoptosis compared with Pha, which may have been driven by the transient G(2)/M cell cycle block which was also observed. These promising results on compound 1 warrant its further investigation as a clinically useful photodynamic therapy agent for head and neck cancer. 相似文献
18.
合成了一系列N9位芳基取代嘌呤-8-酮类衍生物, 利用核磁共振氢谱(1H NMR)、 核磁共振碳谱(13C NMR)和高分辨质谱(HRMS)进行了结构确证. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物的体外抗肿瘤细胞增殖活性. 结果表明, 嘌呤酮环的C2位及N9位的取代对活性有较大影响, C2位引入对位由含氮六元环取代的苯胺, N9位引入对三氟甲基苯均有利于提高抗肿瘤活性. 化合物12c对人白血病细胞(K562)、 人前列腺癌细胞(PC-3)、 人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT116)的抑制效果明显优于阳性对照药R-Roscovitine. 相似文献
19.
甜茶苷是一种自然界中含量稀少的甜味剂。 本实验从多种糖苷酶中筛选出一种来自Aspergillus niger的β-葡萄糖苷酶,用以特异性水解斯替夫苷而高通量制备甜茶苷。 最适条件下反应12 h后,甜茶苷的产率为90.4%,斯替夫苷的转化率达98.8%。 为了进一步考察甜茶苷的安全性并拓展其潜在的用途,实验考察了甜茶苷对人胃肠道和肝脏细胞的细胞毒性,即甜茶苷对3种正常细胞以及11种癌细胞生长的抑制效果。 实验结果表明,在250 μg/mL的质量浓度下,甜茶苷对正常人胃肠肝细胞无毒性;相同质量浓度下,甜茶苷对人体肝癌细胞BEL-7404的抑制率是5-氟尿嘧啶的30%。 相似文献