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1.
Kimatrai M Conejo-García A Ramírez A Andreolli E Da Silveira-Gomes A García MA Aránega A Marchal JA Campos JM 《ChemMedChem》2011,6(10):1854-1859
Herein we report the design, synthesis, and anticancer activity of a series of substituted (R,S)-9-[2- or 3-(3,4-dihydro-2H-1,5-benzoxathiepine-3-yloxy)alkyl]-9H-purines. Derivatives with propylenoxy-linked 2',6'-dichloro- and 6'-bromopurines are more active than their respective ethylenoxy-linked purine conjugates. On the other hand, the compound with a propylenoxy-linked 6'-chloropurine is nearly equipotent to the corresponding ethylenoxy-linked conjugate. Our results show that bromo- and chloropurine-conjugated benzoxathiepines containing a propylenoxy linker are able to inhibit PI3 kinase (PI3K) phosphorylation in MCF-7 breast cancer cells, indicating that the activation of eIF2α, together with inhibition of the PI3K pathway, is the mechanism of action by which these compounds effect their antitumor activity in the MCF-7 cell line; apoptosis was induced in a p53-independent manner. 相似文献
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A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: <0.008-0.5 μg mL(-1)) against the tested Gram-positive strains including MRSA and MRSE than levofloxacin (LVFX, MIC: 0.125-8 μg mL(-1)). Their activity is similar to that of gemifloxacin (GMFX, MIC: <0.008-4 μg mL(-1)). However, they are generally less active than the two reference drugs against Gram-negative strains. Moreover, against clinical strains of S. aureus including MRSA and S. epidermidis including MRSE, the MIC(50) values (0.06-16 μg mL(-1)) and MIC(90) values (0.5-32 μg mL(-1)) of compounds 16 w, y, and z are 2-8- and 2-16-fold less than LVFX, respectively, and 16 w (MIC(90) range: 0.5-4 μg mL(-1)) was also found to be more active than GMFX (MIC(90) range: 1-8 μg mL(-1)). 相似文献
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Mostafa M. Ghorab Marwa G. El-Gazzar Mansour S. Alsaid 《International journal of molecular sciences》2014,15(4):5582-5595
A series of 4-(substituted)-N-(guanidinyl)benzenesulfonamides bearing biologically active pyrazole, pyrimidine and pyridine moieties were prepared and evaluated for their anticancer activity against human tumor breast cell line (MCF7). These sulfonamides showed promising activity with IC50 values ranging from 49.5 to 70.2 μM. The structure-activity relationship of the synthesized compounds was studied. Interestingly, it was found that the most potent compounds in this study were the corresponding 2-cyanoacrylate 3, 3-oxobutanoate 4, pyrazole 6, pyridine 9 and pyrazole 13. Compounds 7 and 8 are nearly as active as Doxorubicin as reference drug with (IC50 values = 70.2, 68.1 μM), while compounds 5, 10 and 11 exhibited a moderate activity. 相似文献
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McKeage MJ Papathanasiou P Salem G Sjaarda A Swiegers GF Waring P Wild SB 《Metal-Based Drugs》1998,5(4):217-223
The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC(50) values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R(*),R(*))-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R(*),R(*))-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models. IC(50) values in the range 0.01 - 0.04 muM were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC(50) data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand. 相似文献
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Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)], [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) and [Rh(2)Cl(2)(mu-OOCCH(3))(terpy)(2)](H(3)O)Cl(2).9H(2)O (R = H, Me, Bu(n), ph, PhCHOH; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (dmp) and 6,7-dimethyl-2,3- di(2-pyridyl)quinoxaline (dmpq); terpy 2,2':6',2'-terpyridine) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Staphylococcus aureus and Escherichia coli has been investigated. The most active antibacterial agents against S. aureus were [Rh(2)(OOCPh)(2)(phen)(2)(H(2)O)(2)](2+), [Rh(2)(OOCPh)(2)(dmpq)(2)(H(2)O)(2)](2+), [Rh(2)(OOCBu)(2)(phen)(2)(H(2)O)(2)](2+) and [Rh(2)-(OOCBu)(2)(bpy)(2)(H(2)O)(2)](2+) which were considerably more active than the appropriate nitrogen ligands. The complexes show rather low activity against E. coli. 相似文献
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Magdalena Peruyska Aleksandra Borzyszkowska-Ledwig Jacek G. Sonicki ukasz Struk Tomasz J. Idzik Gabriela Maciejewska ukasz Skalski Katarzyna Piotrowska Pawe ukasik Marek Dro
dzik Mateusz Kurzawski 《International journal of molecular sciences》2021,22(5)
Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine analogue (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC50 equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells. 相似文献
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Stefan Schulz Wittko Francke Wilfried A. König Volker Schurig Kenji Mori Rolf Kittmann Dietrich Schneider 《Journal of chemical ecology》1990,16(12):3511-3521
(R)-6-Ethyl-2-methyl-2,3-dihydro-4H-pyran-4-one, (1R,3S,5R)-3-ethyl-1,8-dimethyl-2,9-dioxabicyclo[3.3. 1]non-7-ene, and (1R,3S,5R)-3-ethyl-1,8-dimethyl-2,9-dioxabicyclo[3.3.1]non-7-en-6-one represent the main components in the male pheromone of the swift moth,Hepialus hecta. The amounts of the three components were 40, 5, and 5 g per male, respectively. Structure elucidation of the compounds was based on spectroscopic data as compared to synthetic reference samples. The absolute configurations were determined by gas chromatography on chiral stationary phases; optically active samples served as reference compounds. Electrophysiological and behavioral experiments with natural material and synthetic samples clearly showed the three heterocyclic compounds to act as pheromones. (E, E)--Farnesene represents the main component of the scent secretion of maleHepialus humuli. 相似文献
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以三氯化磷、邻苯基苯酚和对苯醌为主要原料,通过三步反应合成了含磷阻燃剂10-(2,5-二羟基苯基)-9,10-二氢-9-氧杂-10-膦菲-10-氧化物(ODOPB)。首先将酯化、酰基化、水解反应连续进行,得到了中间体2-(2-羟基苯基)苯基膦酸(HPPA),收率92.5%。然后HPPA分子内脱水成环反应得到9,10-二氢-9-氧杂-10-膦菲-10-氧化物(DOPO),收率93.2%。最后DOPO与对苯醌进行加成反应得到ODOPB,收率90.2%。三步合成总收率77.8%。HPPA的合成原料配比为n(三氯化磷)∶n(邻苯基苯酚)=1.3,以三氯化磷部分加入部分滴加的方式,且n(直接加入三氯化磷)∶n(滴加三氯化磷)=5.5,于150~200℃滴加反应。用红外光谱、元素分析、核磁氢谱、质谱对产物进行了表征。ODOPB已在覆铜板环氧树脂中成功应用,该合成方法已申请国家专利,正在进行产品中试。 相似文献
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W. Werner D. Tresselt W. Ihn G. Ziebell 《Advanced Synthesis \u0026amp; Catalysis》1987,329(6):1031-1037
Resolution of the Enantiomers of (S,R)-1,1′-Bi-2,2′-naphthylhydrogenphosphate by (1R,2R)- and (1S,2S)-2-Amino-1-(4-nitrophenyl)-propane-1,3-diol The resolution of the diastereoisomeric salts of the title compounds was possible in the presence of a ketone, especially acetone, which forms oxazolidines ( 3a–d ) with the chiral bases. These oxazolidines afforded separable salts with the (S,R)-1,1′-Bi-2,2′-naphthylhydrogenphosphate ( 4 ). The structures of these salts were proved by m.s. and n.m.r. spectroscopy. 相似文献
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以1-乙基-3-(3-二甲胺丙基)碳二亚胺盐酸盐(EDCI)/1-羟基苯并三氮唑(HOBt)为缩合剂,5-氟尿嘧啶-1-基乙酸为中间体,分别与L-酪氨酸甲酯和D-酪氨酸乙酯通过液相偶联合成了(S)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H)-基)乙酰氨基)-3-(4-羟苯基)丙酸甲酯和(R)-2-(2-(5-氟-2,4-二氧-3,4-二氢嘧啶-1(2H)-基)乙酰氨基)-3-(4-羟苯基)丙酸乙酯,水解后得到相应的酸对映体。所合成的化合物结构经1H NMR1、3C NMRI、R、MS及比旋光度等测试得以确证。四种化合物的体外抗肿瘤活性测试结果,说明该化合物的抗肿瘤具有一定的选择性,且R构型对抗肿瘤也起到了一定的作用。 相似文献
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Dr. Ramesh Dasari Andrzej Błauż Derek C. Medellin Roaa M. Kassim Carlos Viera Maximo Santarosa Alet E. van der Westhuyzen Prof. Willem A. L. van Otterlo Taryn Olivas Dr. Tugba Yildiz Prof. Tania Betancourt Prof. Charles B. Shuster Prof. Snezna Rogelj Dr. Błażej Rychlik Prof. Todd Hudnall Prof. Liliya V. Frolova Prof. Alexander Kornienko 《ChemMedChem》2019,14(3):322-333
Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure–activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents. 相似文献
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Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] {R = H, Me; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen)} and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) (R = Me, Et;) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Escherichia coli and Staphylococcus aureus has been investigated. The most active antibacterial agents against E. coli were [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) {R = H and Me} which were considerably more active than the appropriate nitrogen ligands. The complexes show low activity against S. aureus. The activity of the complexes [Rh(2)(OOCR)(2)(N-N)(2)(H(2)O)(2)](OOCR)(2) against E. coli decreases in the series: R=H congruent withCH(3)>C(2)H(5)>C(3)H(7) congruent withC(4)H(9). The reverse order was found in the case of S. aureus. 相似文献
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《Inorganic chemistry communications》2003,6(6):646-649
1,1,1-Trifluoro-4-methoxy-4-aryl-but-3-en-2-ones react with 2-pyridylcarboxamidrazone to produce the corresponding 1,1,1-trifluoro-4-aryl-4-(N1-pyridine-2-carboxamidrazone)-3-buten-2-ones. The butenones react with copper(II) chloride to give 1:1 adducts, in which the donor molecules were shown to isomerize to their cyclic pyrazolic forms. The crystal structure of the 4-fluoro-phenyl derivative, dichloro-[3-(4-fluorophenyl)-1-(imino-pyridin-2-yl-methyl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-pyrazole]-copper(II), was solved by X-ray crystallography. The structural results are compared with those of other copper(II) chloride adducts of similar ligands containing the amidrazone pharmacophore, which have been tested as anticancer drugs. 相似文献
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Yi-Shyan Chen Shu-Mei Lee Chih-Chien Lin Chia-Yi Liu 《International journal of molecular sciences》2014,15(1):1201-1215