共查询到20条相似文献,搜索用时 15 毫秒
1.
Sujay Laskar Manuel López-Ortiz Hugo López-Muñoz María L. Escobar-Sánchez Arturo T. Sánchez 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1129-1135
Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity on cervical cancer cell line (CaSki), breast cancer cell line (MDA-MB231), lung cancer cell line (SK-Lu-1) and human lymphocytes. Among the synthesized dithiocarbamates, compound 9e displayed significant antiproliferative activity without inducing any necrotic cell death (both on tumour cells and lymphocytes) and induced apoptosis in tumor cells by the caspase dependent apoptotic pathway. The compound 9e also exhibited greater tumor selectivity than human lymphocytes. In silico ADME predictions revealed that compound 9e has the potential to be developed as a drug candidate. Rapid chemical modifications of this lead are thus highly necessary for further investigation as a drug like safer antitumor candidate and also to achieve compounds with better activity profile. 相似文献
2.
Cuca LE Coy ED Alarcón MA Fernández A Aristizábal FA 《Biomédica : revista del Instituto Nacional de Salud》2011,31(3):335-343
Introduction. The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia. Objective. To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7. Materials and methods. Fourteen natural compounds were isolated by chromatographic techniques from three native colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining. Results. Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively. Conclusion. Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development. 相似文献
3.
Nuno Vale Ana Correia-Branco Bárbara Patrício Diana Duarte Fátima Martel 《Bioorganic & medicinal chemistry letters》2017,27(15):3507-3510
The investment in cancer research is critical to find more and better treatments, but essentially to save lives. Here, we describe the synthesis and characterization on new bromothiazole derivatives with amino acids and with core of nitazoxanide, an FDA-approved antiprotozoal drug. Using a human adenocarcinoma-derived cell line (the Caco-2 cell line), we then investigated the antiproliferative (3H-thymidine incorporation) and cytotoxic (extracellular lactate dehydrogenase activity) effect of these derivatives. All the derivatives caused a concentration–dependent decrease in cell proliferation and viability. At their highest concentration, all compounds were able to reduce 3H-thymidine incorporation by more than 80%, corresponding to a more marked antiproliferative effect than butyrate. As to their cytotoxic effect, it was comparable to that of butyrate. The ability of bromo substituent in thiazole ring with new sequences of amino acids in inducing cell death and apoptosis in Caco-2 cells (and other cell lines) is now being studied. 相似文献
4.
Meliha Burcu Gürdere Ali Aydin Belkz Yencilek Fatih Ertürk Ouz
zbek Sultan Erkan Yakup Budak Mustafa Ceylan 《化学与生物多样性》2020,17(7)
Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT‐DNA. Most of the enamine derivatives with IC50 values of 86–168 μM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5‐fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (~6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M?1–2.3×104 M?1. The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines. 相似文献
5.
Haga T Uchide N Tugizov S Palefsky JM 《Apoptosis : an international journal on programmed cell death》2008,13(1):97-108
Multicellular tumor spheroids (MCTS) are three dimensional cell culture systems induced by suspension culture. MCTS are widely
used in cancer research because of their similarity to solid tumors. CaSki cells are derived from a metastatic cervical cancer
containing human papillomavirus 16 (HPV16). Cell death of CaSki cells in MCTS has been previously reported, and our model
is used to better characterize the mechanisms of cell death of HPV16-positive keratinocytes. In this study, we found that
apoptosis of CaSki cells was induced by suspension culture along with the formation of MCTS after 24 h of incubation. In suspended
CaSki cells, monoclonal antibodies blocking E-cadherin function inhibited MCTS formation and suppressed suspension-induced
apoptosis in a dose-dependent manner. Western blot for E-cadherin detected upregulation of the authentic 120 kDa band from
MCTS of CaSki cells as well as a shorter 100 kDa band. Addition of EGF, whose receptor is known to form a complex with E-cadherin,
abrogated apoptosis of suspended CaSki cells in a dose-dependent manner. These findings suggest that E-cadherin-dependent
cell–cell contact, directly or indirectly, mediates the signal to undergo apoptosis of CaSki cells during MCTS formation,
and thus provides new information on the role of E-cadherin in cervical cancer cell apoptosis. 相似文献
6.
Kraicheva I Tsacheva I Vodenicharova E Tashev E Tosheva T Kril A Topashka-Ancheva M Iliev I Gerasimova Ts Troev K 《Bioorganic & medicinal chemistry》2012,20(1):117-124
A new Schiff base, 9-anthrylidene-furfurylamine and three novel anthracene-containing α-aminophosphonates, [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine, [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were synthesized. The compounds have been characterized by elemental analysis, TLC, IR, NMR and fluorescent spectra. The aminophosphonates and their synthetic precursors were tested for in vitro antitumor activity on a panel of seven human epithelial cancer cell lines. Safety testing was performed both in vitro (3T3 NRU test) and in vivo on ICR mice for genotoxicity and antiproliferative activity. 9-Anthrylidene-furfurylamine and [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were most potent cytotoxic agents towards colon carcinoma cell line HT-29. The latter compound exhibited also antiproliferative activity to HBL-100, MDA-MB-231 and 647-V cells. The aminophosphonate [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and its synthetic precursor 9-anthrylidene-p-toluidine were found to be cytotoxic to HBL-100 and HT-29 tumor cell lines, respectively. Moderate genotoxic and antiproliferative activity in vivo and low toxicity to Balb/c 3T3 (clone 31) mouse embryo cells were observed for all tested compounds. The subcellular distribution of two tested compounds in a tumor cell culture system was also studied. 相似文献
7.
8.
González-Vadillo AM Alvarez-Valdés A Moneo V Blanco F Díaz RG Carnero A Navarro-Ranninger C 《Journal of inorganic biochemistry》2007,101(4):551-558
The new trans-Pt complexes, derived from trans-[PtCl2(amine)(dimethylamine)] and trans-[PtCl2(OH)2(amine)(dimethylamine)], were synthesized and characterized studying the structure-activity relationship and testing their antiproliferative activity. Their evaluation as cytotoxic agents towards different cancer and normal cell lines is presented. These compounds are active in a panel of tumor cell lines at low micromolar range. Compounds seems to be more active in tumoral than in normal primary human cell lines. Cytotoxic activity is closely related to the amine ligand. Cyclohexylamine ligand was the most active among the amine-ligands tested. Cytotoxic activity correlates with an increase in annexin V positive cells indicating an apoptotic effect of the compounds. Mechanistically, the antitumor activity correlates with a blockade of the cell cycle in S phase and a complete abolishment of G2/M checkpoint arrest suggesting physical interaction of compound with DNA inhibiting S phase transition. 相似文献
9.
Tuba Kul Kprülü Salih
kten aban Tekin Osman akmak 《Journal of biochemical and molecular toxicology》2019,33(3)
Due to a great deal of biological activities, quinoline derivatives have drawn attention for synthesis and biological activities in the search for new anticancer drug development. In this work, a variety of substituted (phenyl, nitro, cyano, N‐oxide, and methoxy) quinoline derivatives ( 3 ‐ 13 ) were tested in vitro for their biological activity against cancer cell lines, including rat glioblastoma (C6), human cervical cancer cells (HeLa), and human adenocarcinoma (HT29). 6‐Bromo‐5‐nitroquinoline ( 4 ), and 6,8‐diphenylquinoline (compound 13 ) showed the greatest antiproliferative activity as compared with the reference drug, 5‐fluorouracil (5‐FU), while the other compounds showed low antiproliferative activity. 6‐Bromo‐5‐nitroquinoline ( 4 ) possesses lower cytotoxic activity than 5‐FU in HT29 cell line. Due to its the apoptotic activity 6‐Bromo‐5‐nitroquinoline ( 4 ) has the potential to cause cancer cell death. 相似文献
10.
Collu F Bonsignore L Casu M Floris C Gertsch J Cottiglia F 《Bioorganic & medicinal chemistry letters》2008,18(5):1559-1562
Two new cyclohexenones (antheminones A and B) and a new cyclohexanone, (antheminone C) along with five known compounds were isolated from the leaves of Anthemis maritima L. The structures were mainly deduced from extensive 1D and 2D NMR spectroscopy and mass spectrometry. The new compounds were tested in vitro for their cytotoxic activity against adherent and non-adherent cancer cell lines. Antheminones A and C exhibited significant antiproliferative activity against leukemia cells with IC(50) values ranging from 3.2 to 14 microM. 相似文献
11.
Reeta Rai Roshan Kumar Dutta Surjeet Singh Dharmendra Kumar Yadav Seema Kumari Harpreet Singh Rinkoo Devi Gupta Ramendra Pratap 《Bioorganic & medicinal chemistry letters》2018,28(9):1574-1580
A series of functionalized naphthalene was synthesized and screened against human prostate cancer cell line (PC-3). The in vitro antiproliferative activity of the synthesized compounds was evaluated by monitoring their cytotoxic effects against PC-3 cells by using MTT assay. We observed that compound 5f resulted in more than 50% cell death at 14?µM. Treatment of PC-3 cells with 5f provides apoptosis by flow cytometry. Western blotting showed decreased expression of pro-caspase 8 and 9. Our study shows that cancer cell treated with 5f has higher concentration of reactive oxygen species as compare to untreated sample, which facilitate cancerous cell to enter apoptosis. Exact mechanism by which ROS is generated after 5f treatment is still under study. Molecular docking study further strengthens the results obtained from in vitro experiments. Compound 5f can be considered as a promising leads for anticancer agent against prostate cancer cells due to its potent cytotoxic activity and apoptotic effect. 相似文献
12.
Resham Lal Gurung Shi Ni Lim Aik Kia Khaw Jasmine Fen Fen Soon Kirthan Shenoy Safiyya Mohamed Ali Manikandan Jayapal Swaminathan Sethu Rajamanickam Baskar M. Prakash Hande 《PloS one》2010,5(8)
Background
A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells.Methodology/Principal Findings
The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs.Conclusions/Significance
Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in the management for brain tumours. 相似文献13.
Tetraarylporphyrins of the Ar:Ar′ = 3:1-type were synthesized from pyrrole, 4-hydroxybenzaldehyde and benzaldehydes substituted with ethyleneglycol, hydroxy and quaternary ammonium substituents for solubilization in DMF and, in particular, in water. After etherification with the tosylate of diethyl cyclobutanedicarboxylate and subsequent ester hydrolysis, the resulting carboxylic acid groups were used to bind platinum fragments bearing two ammonia and (RR/SS)-trans-1,2-diaminocyclohexane ligands, respectively, as non-leaving groups. In comparison to hematoporphyrin-platinum complexes, the title compounds show a 30 nm bathochromic shift of their absorption bands increasing the penetration depth of the red light used for irradiation in photodynamic tumor therapy. The antiproliferative activity of 24 new platinum complexes differing in the porphyrin ligands and the platinum fragments were studied in tests with J82 bladder cancer cells. The compounds showed the cytotoxic effect of the platinum moiety and after irradiation the phototoxic effect of the porphyrin system. 相似文献
14.
A new series of novel Podophyllotoxin-like benzo[b]furo[3,4-e][1,4]diazepin-1-ones possessing structural elements of 4-aza-2,3-didehydropodophyllotoxins with central diazepine ring was designed and synthesized as anti-cancer agents. In initial assessment, the cytotoxic activity of the synthesized compounds was evaluated against three cancer cell lines including MCF-7, PC3 and B16-F10 employing the MTT assay. Some of compounds (12h, 13a, 13c and 14b) showed significant cytotoxic activity. So, we investigated the cytotoxicity of compounds 12h, 13a, 13c and 14b, along with podophyllotoxin as the reference drug in different cancer cell lines including A549, A2780, DU145, HeLa, and normal Huvec cell line. Among these four compounds, 13c showed promising antiproliferative activity against all cancer cells stronger than the other compounds and comparable to reference drug podophyllotoxin in some cancer cells. All these four compounds did not show significant cytotoxicity on normal Huvec cell line. The flow cytometry analysis of the MCF-7, PC3 and A2780 human cancer cell lines treated with 13c showed that 13c, induced apoptosis in the MCF-7, PC3 and A2780 human cancer cell lines, which is in good agreement to its cytotoxic activity as well. Compound 13c did not show significant influence on tubulin assembly and exert its cytotoxic effects via induction of apoptosis and has potent and selective cytotoxic effects in cancer cells. 相似文献
15.
Caspase-independent autophagic cytotoxicity in etoposide-treated CaSki cervical carcinoma cells 总被引:2,自引:0,他引:2
We studied the in vitro mechanism of etoposide-induced cell death in cervical cancer cells. Etoposide is cytotoxic to these cells, causing cell death by both apoptosis and autophagy, which has recently been described as a possible mechanism for nonapoptotic cell death. Electron microscopy revealed that autophagosomes/autolysosomes exhibited an autophagic appearance in the presence of etoposide. When autophagy was blocked by inhibitors of autophagy, including 3-methyladenine, both the expression of beclin 1 protein and the antitumor effect of etoposide were suppressed. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a pan-caspase inhibitor, reduced etoposide-induced cytotoxicity in CaSki cells. Hence, autophagy and apoptosis likely occur concurrently in etoposide-treated cervical cancer cells. 相似文献
16.
Davis DD Díaz-Cruz ES Landini S Kim YW Brueggemeier RW 《The Journal of steroid biochemistry and molecular biology》2008,108(1-2):23-31
Natural isoflavones have demonstrated numerous pharmacological activities in breast cancer cells, including antiproliferative activities and binding affinities for estrogen receptors (ERs). Chemical modifications on the isoflavone ring system have been prepared and explored for the development of new therapeutics for hormone-dependent breast cancer. The antiproliferative actions of the synthesized isoflavones on MCF-7 and MDA-MB-231 breast cancer cells were examined, as well as cytotoxicity, interaction with estrogen receptors, and proapoptotic activity. The compounds were screened in the absence and in the presence of estradiol to evaluate whether or not estradiol could rescue cell proliferation on MCF-7 cells. Several compounds were able to inhibit cell proliferation in a dose-dependent manner, and compounds containing the bulky 7-phenylmethoxy substituent resulted in cell toxicity not only in MCF-7 cells but also in MDA-MB-231 cells. Selected synthetic isoflavones were able to bind to estrogen receptor with low affinity. Apoptotic pathways were also activated by these compounds in breast cancer cells. The majority of the compounds can bind to both ERs with low affinity, and their effects on hormone-independent breast cancer cells suggest that their ability to inhibit cell growth in breast cancer cells is not exclusively mediated by ERs. Thus, the synthetic trisubstituted isoflavones act on multiple signaling pathways leading to activation of mechanisms of cell-death and ultimately affecting breast cancer cell survival. 相似文献
17.
A cornucopia of physiological and pathological circumstances including anticancer chemotherapy and radiotherapy can induce cell death. However, the immunological consequences of tumor cell demise have remained largely elusive. The paradigm opposing 'apoptosis versus necrosis' as to their respective immunogenicity does not currently hold to predict long-term immunity. Moreover, the notion that tumor cells may be 'stressed' before death to be recognized by immune cells deserves to be underlined. 'Eat-me', 'danger' and 'killing' signals released by stressed tumor under the pressure of cytotoxic compounds may serve as links between the chemotherapy-elicited response of tumor cells and subsequent immune responses. This review will summarize the state-of-the-art of cancer immunity and describe how tumor cell death dictates the links between innate and acquired immunity. 相似文献
18.
E Lotzová 《Natural immunity and cell growth regulation》1990,9(4):253-264
We have analyzed the anticancer efficacy of various subsets of human circulating and tumor-infiltrating lymphocytes (TIL). These studies showed that circulating natural killer (NK) cells mediate the most potent oncolytic activity against a variety of tumor targets, after enrichment or stimulation with interleukin-2 (IL-2). Interestingly, NK cell oncolytic activity was directed also against tumor targets frequently designated as 'NK-resistant'. This indicates that NK cells display a broader spectrum of killing than is commonly recognized. TIL did not display any tumoricidal activity when unstimulated, but acquired cytotoxic potential after activation with IL-2. Comparative studies of TIL and circulating lymphocytes from patients with ovarian cancer demonstrated that these two groups of lymphocytes manifested similar levels of cytotoxicity and the same spectrum of target cell killing. No specificity in autologous tumor cell killing was displayed by TIL; instead, TIL were effective against autologous as well as allogeneic tumor targets. The lack of TIL tumor specificity was not detected only in ovarian tumors, but was manifested also in renal- and squamous-cell cancers. Characterization studies demonstrated that the primary oncolytic cells in the periphery and among TIL are NK cells. T lymphocytes displayed some, but rather negligible cytotoxic activity. In contrast, when IL-2-activated NK and T cells were analyzed for lytic activity against normal hematopoietic cells, T cells displayed high levels of bone marrow killing. The anti-bone marrow lytic activity of IL-2-activated T lymphocytes may be harmful after therapy with conventionally prepared lymphokine-activated killers. In light of these observations, new directions to adoptive immunotherapy are discussed. 相似文献
19.
Using cholesterol, β-sitosterol, dehydroisoandrosterone and pregnenolone as starting materials, a series of 5(6→7)abeo-sterols with different substituted groups and various side chains were synthesized and the antiproliferative activity of these compounds against HeLa, SMMC 7404 and MGC 7901 cells was investigated. The results revealed that the presence of a cholesterol-type side chain was very important for their cytotoxicity, and in particular a thiosemicarbazone at the C-6 position significantly enhanced the antiproliferative activity of these compounds. Although the elimination of 5-hydroxyl has no an obvious effect on their cytotoxic function, removal of the hydroxyl at the C-3 position decreased markedly the antiproliferative activity of the compounds. Some compounds have similar cytotoxic capability as cisplatin does. 相似文献
20.
Pires VS Gaboriau F Guillon J Nascimento S Dassonville A Lescoat G Desplat V Rochette J Jarry C Sonnet P 《Journal of enzyme inhibition and medicinal chemistry》2006,21(3):261-270
Cell cycle progression is dependent on intracellular iron level and chelators lead to iron depletion and decrease cell proliferation. This antiproliferative effect can be inhibited by exogenous iron. In this work, we present the synthesis of new synthetic calix[4]arene podands bearing two aspartic/glutamic acid, ornithine groups or hydrazide function at the lower rim, designed as potential iron chelators. The synthesis only afforded calix[4]arenes in the cone conformation. We report their effect on cell proliferation, in comparison with the new oral chelator ICL670A (4-[3,5-bis-(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid). The antiproliferative effect of these new compounds was studied in the rat hepatoma cell line Fao by measuring mitochondrial succinate dehydrogenase activity. Their cytotoxicity was evaluated by extracellular LDH activity. Preliminary results indicated that among all tested compounds, monohydrazidocalix[4]arene 2 which is not cytotoxic in Fao cells exhibits interesting antiproliferative activity. This effect, independent on iron depletion, remains to be further explored. Moreover, it also shows that new substituted calix[4]arenes could open the way to new valuable medicinal chemistry scaffolding. 相似文献