共查询到20条相似文献,搜索用时 31 毫秒
1.
《Bioorganic & medicinal chemistry letters》2014,24(1):136-140
The synthesis and characterization of some new titanocene-complexes, having a ethenyl-phenoxide or a benzyl group as substituents of the cyclopentadienyl rings, are reported. The synthesized compounds have been evaluated for their cytotoxic potential against two human breast cancer cell lines, that is: MCF7 and SkBr3. Most of these compounds have shown significant cytotoxic effects, compared to cisplatin, in MTT-based cell tests. 相似文献
2.
Silva H Valério Barra C França da Costa C de Almeida MV César ET Silveira JN Garnier-Suillerot A Silva de Paula FC Pereira-Maia EC Fontes AP 《Journal of inorganic biochemistry》2008,102(4):767-772
This work describes the synthesis and characterization of four new ligands derived from 1,3-propanediamine in addition to the preparation and characterization of their respective platinum(II) complexes by reaction with K2PtCl4. These ligands were obtained by the reaction of the corresponding alkyl mesylate with 1,3-propanediamine. We have prepared compounds having different carbon chains lengths in an attempt to correlate this factor, which influences the lipophilicity of the compounds, with cytotoxic activity. Octanol/water partition coefficients, the effect of the four complexes on the growth of two tumoral cell lines, and their cellular uptake were investigated. Increasing lipophilicity enhances the rate of cellular uptake and, consequently, the cytotoxic activity. 相似文献
3.
Evolution and current status of research in phenolic compounds 总被引:4,自引:1,他引:3
Boudet AM 《Phytochemistry》2007,68(22-24):2722-2735
4.
Exploring the physicochemical and antiproliferative properties of biaryl-linked [13]-macrodilactones
《Bioorganic & medicinal chemistry》2020,28(20):115671
A macrocyclic motif fosters productive protein-small molecule interactions. There are numerous examples of both natural product and designed, synthetic macrocycles that modulate the immune system, slow microbial infection, or kill eukaryotic cells. Reported here are the synthesis, physicochemical characterization, and antiproliferative activity of a group of [13]-macrodilactones decorated with a pendant biaryl moiety. Biaryl analogs were prepared by Suzuki reactions conducted on a common intermediate that contained a bromophenyl unit alpha to one of the carbonyls of the [13]-macrodilactone. Principal component analysis placed the new compounds in physicochemical context relative to a variety of pharmaceuticals and natural products. Modest inhibition of proliferation was observed in ASZ cells, a murine basal cell carcinoma line. This work underscores the value of an approach toward the identification of bioactive compounds that places the evaluation of physicochemical parameters early in the search process. 相似文献
5.
Nazia Tambat Pranav Tambe Amin Shaikh Kounsar N. Shiekh Leonhard H. F. Köhler Rainer Schobert Bernhard Biersack Khursheed Ahmed 《化学与生物多样性》2023,20(8):e202300149
We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness. Among the nine compounds tested, four compounds (5 a, 5 d, 5 g, and 5 h) exhibited promising antiproliferative activity specifically against HCT-116 p53-negative cells (IC50 0.23, 0.20, 2.07 and 58.75 μM, respectively). Interestingly, treatment with the 3,4-dimethoxyphenyl derivative 5a resulted in a significant increase (199 %) in caspase activity in HCT-116 p53-negative cells compared to untreated cells while the bromo-pyrazine derivative 5d demonstrated (190 %) increase. These findings suggest that compounds 5a and 5 d induce p53-independent apoptotic cell death. Additionally, in silico molecular docking studies with EGFR and tyrosinase proteins indicated that compounds 5 d and 5 e have the potential to bind to important anticancer drug targets. 相似文献
6.
Romina E. Avanzo José M. Padrón Norma B. DAccorso Mirta L. Fascio 《Bioorganic & medicinal chemistry letters》2017,27(16):3674-3677
The emergence of multidrug resistance cell lines is one of the major obstacles in the success of cancer chemotherapeutic treatment. Therefore, it remains a big challenge the development of new and effective drugs to defeat cancer. The presence of nitrogen heterocycles in the architectural design of drugs has led to the discovery of new leading compounds. Herein, we report the synthesis, characterization and in vitro antiproliferative activity against six cancer cell lines of d-ribofuranoside derivatives bearing a 1,2,4-oxadiazolic ring, with the aim of developing new active compounds. Most of these derivatives exhibit significant antiproliferative activities in the micromolar range. Noteworthy, the most potent compound of the series showed better selectivity towards the more resistant colon cancer cell line WiDr. 相似文献
7.
A new series of steroidal dihydrocarbothioic acid amido pyrazole analogues were synthesized, and after characterization, evaluation for cytotoxicity, comet assay and western blotting was carried out. The synthesis of these analogues is convenient and involves two steps, i.e. aldol condensation as first step followed by nucleophilic addition of thiosemicarbazide across α, β-unsaturated carbonyl as a later step. Quantitative yields of more than 80 % are obtained in both the steps. After characterization by IR, 1H NMR, 13C NMR, MS and analytical data, all the compounds of both series were tested for cytotoxic activity against a panel of different human cancer cell lines by MTT assay, during which compound 3e, 3f, 4e, 4f and 4h are very potent especially against HepG2 and MCF-7 cancer cell lines. Cell cycle analysis depicted the cell death in S-phase while as annexin V-FITC/PI analysis showed that compounds effectively induce apoptosis. Apoptotic degradation of DNA of MCF-7 cells in the presence of different steroidal derivatives was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). In western blotting analysis, the relative expressions of relevant apoptotic markers depicted an apoptosis by steroidal dihydropyrazole in MCF-7 cancer cells. 相似文献
8.
Apoptosis induction and inhibition of H-ras overexpression by novel trans-[PtCl2(isopropylamine)(amine')] complexes 总被引:1,自引:0,他引:1
Pérez JM Montero EI González AM Alvarez-Valdés A Alonso C Navarro-Ranninger C 《Journal of inorganic biochemistry》1999,77(1-2):37-42
Hitherto, it has been generally accepted as a paradigm of the biochemical pharmacology of platinum antitumor drugs that a cis configuration of the leaving groups is necessary for antitumor activity of platinum compounds. However, it has been recently observed that certain trans-platinum complexes have both in vitro and in vivo antitumor activity. We previously reported the synthesis, characterization and cytotoxic activity against ras-transformed cells of several trans-[PtCl2LL'] complexes where L and L' are asymmetric aliphatic amines (L = dimethylamine and butylamine, L' = isopropylamine). The results reported in this paper show that the compounds trans-[PtCl2(isopropylamine)(dimethylamine)] and trans-[PtCl2(isopropylamine)(butylamine)] kill Pam 212-ras cisplatin resistant cells through apoptosis induction. Moreover, Western blot data show that both compounds inhibit overexpression of H-ras oncogene in Pam 212-ras cells. Altogether, these data indicate that, in contrast with cis-DDP, the apoptotic activity of these novel trans-Pt(II) compounds in ras-transformed cells is associated with their ability to abolish ras-overexpression. 相似文献
9.
Biosynthesis and properties of the plant cell wall 总被引:11,自引:0,他引:11
Reiter WD 《Current opinion in plant biology》2002,5(6):536-542
The characterization of cell wall mutants of Arabidopsis thaliana, combined with biochemical approaches toward the purification and characterization of glycosyltransferases, has led to significant advances in understanding cell wall synthesis and the properties of cell walls. New insights have been gained into the formation of cellulose and the functions of the matrix polysaccharides rhamnogalacturonan-II and xyloglucan. 相似文献
10.
Plants need an enormous biosynthetic machinery to synthesize the complex polysaccharides that are present in the plant cell wall. The isolation, characterization and mapping of wall mutants, together with biochemical approaches, have led to significant advances in our understanding of both wall polysaccharide synthesis at a molecular level and the function of polysaccharides in plant growth and development. Moreover, potential regulation mechanisms and associated protein factors are emerging from recent data. 相似文献
11.
Abdullaev FI Rivera-Luna R García-Carrancá A Ayala-Fierro F Espinosa-Aguirre JJ 《Mutation research》2001,493(1-2):31-38
Numerous epidemiological studies suggest that arsenic (As) compounds are carcinogens, however, recent data have renewed the interest in their anticarcinogenic properties. The cytotoxic effects of three arsenic compounds were assessed: sodium arsenite, sodium arsenate and sodium cacodylate, representing the trivalent and pentavalent species of arsenic, along with a dimethylated pentavalent arsenic species. HeLa cells and Salmonella typhimurium (strains TA98 and TA100) were exposed to As compounds and the cytotoxic effects were evaluated. Alterations on RNA and DNA synthesis in HeLa cells were also examined. All arsenic compounds produced a dose-dependent inhibition on colony formation and DNA synthesis in HeLa cells, yet any of them significantly influenced RNA synthesis in these cells. No evidence of arsenic-induced mutagenicity or antimutagenicity was observed using the Ames assay. In bacterial cells, only sodium arsenite caused a dose-dependent inhibition of colony formation.Collectively, these results indicate that in both, HeLa and S. typhimurium cell systems, only trivalent sodium arsenite can act as an effective inhibitor of cell growth. The possible mechanism(s) of the cytotoxic effect of arsenite in these two different cell systems might be due to its reactivity with intracellular sulfhydryl groups. 相似文献
12.
Belicchi Ferrari M Bisceglie F Pelosi G Sassi M Tarasconi P Cornia M Capacchi S Albertini R Pinelli S 《Journal of inorganic biochemistry》2002,90(3-4):113-126
Synthesis and characterization of new thiosemicarbazones derived from natural aldehydes (1–9) have been investigated in order to develop a research program aimed at the development of compounds with antiviral, antibacterial, and antitumor properties. These substances contain both a chain with N and S nucleophilic centers with tuberculostatic activity, and an alkyl or terpenic moiety. In addition, a few nickel(II) and copper(II) complexes (10–18), derived also from the previously studied ligands, were synthesized and characterized by means of NMR and IR techniques. The trans-2-octenal N1-phenylthiosemicarbazone and its nickel complex were also characterized by X-ray diffractometry. Biological studies, performed with some of these compounds, have involved both inhibition of cell proliferation and apoptosis tests in vitro on human leukemia cell line U937 to deepen our knowledge on the way these substances interfere with biological processes in leukemic cells. 相似文献
13.
Leonard M. Patt William J. Grimes 《Biochimica et Biophysica Acta (BBA)/General Subjects》1976,444(1):97-107
A mannosyltransferase has been detected in suspensiosn of BALB/c fibroblasts incubated with GDP-[14C]mannose. The experimental evidence indicates the cell surface as the most likely site for the enzyme. The transferase synthesizes both glycolipids and glycoproteins. The lipid compounds have properties suggestive of lipid-linked mono- and oligosaccharides which can function as intermediates in glycoprotein synthesis. The formation of these compounds by a cell surface enzyme suggests that lipid-linked intermediates may play an important role in the glycosylation of membrane components. 相似文献
14.
Peptidyl methylcoumarin amides are well established as model substrates for understanding protease specificity, but the corresponding methylcoumarin esters have attracted scant attention despite their potential utility in active-site titration and mechanistic characterization. We have devised techniques for the synthesis and deprotection of extended peptidyl methylcoumarin esters in good to moderate yields, and we have demonstrated their suitability for steady-state characterization and active-site titration of the Saccharomyces cerevisiae processing protease Kex2. Additionally, we have used one of these compounds to active-site titrate the homologous enzyme PC2, which had not previously been feasible using other types of substrates. These compounds should thus prove widely suitable for use as substrates and active-site titrants not only for proteases of the prohormone processing family but also for a wide range of other serine proteases. 相似文献
15.
Kamal A Mallareddy A Suresh P Shaik TB Lakshma Nayak V Kishor C Shetti RV Sankara Rao N Tamboli JR Ramakrishna S Addlagatta A 《Bioorganic & medicinal chemistry》2012,20(11):3480-3492
A series of chalcone-amidobenzothiazole conjugates (9a-k and 10a,b) have been synthesized and evaluated for their anticancer activity. All these compounds exhibited potent activity and the IC(50) of two potential compounds (9a and 9f) against different cancer cell lines are in the range of 0.85-3.3 μM. Flow cytometric analysis revealed that these compounds induced cell cycle arrest at G2/M phase in A549 cell line leading to caspase-3 dependent apoptotic cell death. The tubulin polymerization assay (IC(50) of 9a is 3.5 μM and 9f is 5.2 μM) and immuofluorescence analysis showed that these compounds effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further, Annexin staining also suggested that these compounds induced cell death by apoptosis. Moreover, docking experiments have shown that they interact and bind efficiently with tubulin protein. Overall, the current study demonstrates that the synthesis of chalcone-amidobenzothiazole conjugates as promising anticancer agents with potent G2/M arrest and apoptotic-inducing activities via targeting tubulin. 相似文献
16.
17.
1,2,4,5-Tetrazines have been established as effective dienes for inverse electron demand [4 + 2] Diels-Alder cycloaddition reactions with strained alkenes for over 50 years. Recently, this reaction pair combination has been applied to bioorthogonal labeling and cell detection applications; however, to date, there has been no detailed examination and optimization of tetrazines for use in biological experiments. Here, we report the synthesis and characterization of 12 conjugatable tetrazines. The tetrazines were all synthesized in a similar fashion and were screened in parallel to identify candidates most ideally suited for biological studies. In depth follow-up studies revealed compounds with varying degrees of stability and reactivity that could each be useful in different bioorthogonal applications. One promising, highly stable, and water-soluble derivative was used in pretargeted cancer cell labeling studies, confirming its utility as a bioorthogonal moiety. 相似文献
18.
The investigation of toxic compounds which need a previous metabolic activation often gets advantage by the employment of cell suspensions, in most of the cases rat hepatocytes. In particular, this model system allows the characterization of lipid peroxidation kinetics, the evaluation of its pathogenetic role in the induction of cell death and the analysis of the interaction among different prooxidant compounds in bringing about both oxidative damage and cytolysis. 相似文献
19.
McNamara YM Cloonan SM Knox AJ Keating JJ Butler SG Peters GH Meegan MJ Williams DC 《Bioorganic & medicinal chemistry》2011,19(3):1328-1348
Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds containing a classic nitrostyrene structure are shown to have antiproliferative activities in vitro in a range of malignant cell lines, particularly against Burkitt's lymphoma derived cell lines, whilst having no effect on 'normal' peripheral blood mononuclear cells. Such effects appear to be independent of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage, chromatin condensation and membrane blebbing in a Burkitt's lymphoma derived cell line, consistent with these compounds inducing apoptosis in vitro. Although no specific target has yet been identified for the action of these compounds, the cell death elicited is potent, selective and worthy of further investigation. 相似文献
20.
N V Myasishcheva E V Quadros D M Matthews J C Linnell 《Biochimica et biophysica acta》1979,588(1):81-88
1. 72 h uptake of cyano[57Co]cobalamin and formation of 57Co-labelled methylcobalamin, adenosylcobalamin and hydroxocobalamin has been estimated with and without the addition of methylcobalamin analogues in phytohaemagglutinin-stimulated lymphocytes from healthy human subjects. 2. Difluorochloromethylcobalamin reduced cell uptake of cyanocobalamin and caused a disproportionate reduction in synthesis of adenosylcobalamin. 3. Methylcobalamin-palladium trichloride reduced cell uptake of cyanobalamin more effectively than did difluorochloromethylcobalamin and reduced the formation of methylcobalamin, adenosylcobalamin and hydroxocobalamin in proportion. 4. The results suggest that in addition to inhibiting uptake of cyanocobalamin, one or both compounds may have interfered directly with the mechanism of synthesis of the cobalamin coenzymes. 相似文献