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1.
Some 4‐anilinofuro[2,3‐b]quinoline derivatives were synthesized from dictamnine, a natural alkaloid, and evaluated for their cytotoxicity in the NCI's full panel of 60 human cancer cell lines derived from nine cancer cell types, including leukemia, non‐small‐cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer. 1‐[4‐(Furo[2,3‐b]quinolin‐4‐ylamino)phenyl]ethanone ( 5 ) (mean GI50=0.025 μM ), bearing an 4‐acetylanilino substituent at C(4) of furo[2,3‐b]quinoline, was more active than its 3‐acetylanilino counterpart 7 (mean GI50=5.27 μM ), and both clinically used anticancer drugs, N‐[4‐(acridin‐9‐ylamino)‐3‐methoxyphenyl]methanesulfonamide (m‐AMSA; mean GI50=0.44 μM ) and daunomycin (mean GI50=0.044 μM ). Compound 5 was capable of inhibiting all types of cancer cells tested with a mean GI50 of less than 0.04 μM in each case except for the non‐small‐cell lung cancer (average GI50=1.75 μM ). Although non‐small‐cell lung cancer is resistant to compound 5 , the sensitivity within this type of cancer cells varies: HOP‐62 (GI50<0.01 μM ), NCI‐H460 (GI50=0.01 μM ), and NCI‐H522 (GI50<0.01 μM ) are very sensitive, while HOP‐92 (GI50 = 12.4 μM ) is resistant. Among these non‐small‐cell lung cancers, NCI‐H522 was found to be very sensitive to 5, 8a , and 8b with a GI50 values of <0.01, 0.074, and <0.01 μM , respectively.  相似文献   

2.
Phenylbutyrate (PB), a small aromatic fatty acid, has been known as an interesting compound with the ability of anti-proliferation and cell growth inhibition in cancer cells. In the present study, a series of PB derivatives were synthesized by Passerini multicomponent reaction and their cytotoxic activities against various human cancer cell lines including A549 (non-small cell lung cancer), MDA-MB-231 (breast cancer), and SW1116 (colon cancer) were evaluated. The results revealed that B9, displayed significantly higher in vitro cytotoxicity with IC50 of 6.65, 8.44 and 24.71 μM, against A549, MDA-MB-231 and, SW1116, respectively, in comparison to PB. The effects of these compounds on the proliferation of MCF-10A as non-tumoral breast cell line, showed good selectivity of the compounds between tumorigenic and non-tumorigenic cell lines. Moreover, B9 has indicated apoptosis-inducing activities to MDA-MB-231 cancer cell line in a dose-dependent manner. The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to predict the binding sites and binding orientation of the compounds to these targets.  相似文献   

3.
A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral (1H NMR, IR, and MS) data and the absolute configuration of compound (II 1 ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evaluated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II 21 (IC50 = 4.7 μM for MCF-7 and IC50 = 9.3 μM for MDA-MB-231), II 33 (IC50 = 2.4 μM for MCF-7 and IC50 = 4.2 μM for MDA-MB-231) and II 40 (IC50 = 3.3 μM for MCF-7 and IC50 =8.6 μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC50 = 4.8 μM for MCF-7 and IC50 = 9.6 μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II 33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II 1 , II 6 , II 11 , II 16 , II 23 , II 28 , and II 35 were also studied and compound II 28 afforded the highest photoluminescence quantum yield (38%).  相似文献   

4.
A series of 28 novel 2‐(4‐aminophenyl)benzothiazole analogues have been synthesized and characterized using various analytical techniques like 1H NMR, 13C NMR, electrospray ionization mass spectrometry, and IR and bioevaluated for their antiproliferative activity over a group of three human cancer cell lines, namely, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MDA‐MB‐231), using sulforhodamine B assay method. Few synthesized molecules ( 5a , 5c , 5d , 5f , 7b , and 7j ) displayed effective growth inhibition (GI50) activity against the tested human cancer cell lines at lower micromolar concentration (GI50) values in the range 0.2–1.7 μM. Noticeably, compound 7b exhibited reasonable activity in all three cancer cell lines in the GI50 range 0.55–1.2 μM. Further, when 7b was screened for tubulin polymerization inhibition, it exhibited more than 55% inhibition at concentration of 5.0 μM. The molecular docking simulations supported the molecular interactions of the derivatives with the targeted receptor. These derivatives may serve as lead structures for development of potential anticancer drug candidates, and 7b might act as a potential microtubule polymerization inhibitor.  相似文献   

5.
Abstract

In this study, two novel benzimidazole-based N-heterocyclic carbene ligands (1a-b) and their silver(I) complexes (2a-b) were synthesized. All new compounds were characterized by FT-IR, LC-MS, 1H NMR, and 13C NMR spectroscopies. The in vitro antitumor activities of NHC ligands (1a-b) and their silver(I) complexes (2a-b) against DU-145 human prostate cancer cells, MDA-MB-231 and MCF-7 human breast cancer cells and L-929 (normal cells adipose from mouse) were also determined using MTT analysis for 24?h, 48?h, and 72?h. The results showed that while NHC ligands did not have in vitro antitumor activity on MCF-7, MDA-MB-231 and DU-145 cells, Ag(I)-NHC complexes have in vitro antitumor activities. The in vitro antitumor activity of 2a was found to be lower than that of 2b. Ag(I)-NHC complexes were observed to have higher IC50 values for non-cancerous cell lines than cancer cells.  相似文献   

6.
A series of novel 5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-thiazolidinones (Ciminalum–thiazolidinone hybrid molecules) have been synthesized. Anticancer activity screening toward the NCI60 cell lines panel, gastric cancer (AGS), human colon cancer (DLD-1), and breast cancer (MCF-7 and MDA-MB-231) cell lines allowed the identification of 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (2h) with the highest level of antimitotic activity with mean GI50/TGI values of 1.57/13.3 μM and a certain sensitivity profile against leukemia (MOLT-4, SR), colon cancer (SW-620), CNS cancer (SF-539), melanoma (SK-MEL-5), gastric cancer (AGS), human colon cancer (DLD-1), and breast cancers (MCF-7 and MDA-MB-231) cell lines. The hit compounds 2f, 2i, 2j, and 2h have been found to have low toxicity toward normal human blood lymphocytes and a fairly wide therapeutic range. The significant role of the 2-chloro-3-(4-nitrophenyl)prop-2-enylidene (Ciminalum) substituent in the 5 position and the substituent’s nature in the position 3 of core heterocycle in the anticancer cytotoxicity levels of 4-thiazolidinone derivatives have been established  相似文献   

7.
Anticancer activity as an associated action for a series of dithiocarbamates of 9,10-anthracenedione was predicted using the PASS computer program and analysed with PharmaExpert software. The predicted cytotoxic activity of the dithiocarbamate derivatives of 9,10-anthracenedione was evaluated in vitro on cancer cells of the human lung (A549), prostate (PC3), colon (HT29) and human breast (MCF7) using the sulforhodamine B (SRB) cell viability assay. Among these compounds, 9,10-dioxo-9,10-dihydroanthracen-1-yl pyrrolidin-1-carbodithioate and 9,10-dioxo-9,10-dihydroanthracen-2-yl pyrrolidin-1-carbodithioate were identified as the most potent anticancer agents with cytotoxic activity against the MCF-7 human breast cell line with GI50 values of 1.40 μM and 1.52 μM, whereas the GI50 value for the reference anticancer drug mitoxantrone was 3.93 μM. Thus, anticancer activity predicted by PASS with a probability Pa > 30% was confirmed by the experiment. Relatively small Pa values estimated by PASS indicated the novelty of the considered derivatives comparing to the compounds from the PASS training set.  相似文献   

8.
Ruthenium tetrazene complexes with general formula [Cp*RuCl(1,4-R2N4)] (Cp* = η5-C5Me5), where R = benzyl ( 1 ), 2-fluorobenzyl ( 2 ), β-d -glucopyranosyl-unprotected ( 3a ) and acyl-protected ( 3b – d ), 2-acetamido-β-d -glucopyranosyl-unprotected ( 4a ) and acyl-protected ( 4b – d ), propyl-β-d -glucopyranoside-unprotected ( 5a ), and O-acetylated ( 5b ), were synthesized and characterized using nuclear magnetic resonance and electrospray ionization–mass spectrometry. In addition, the molecular structure of 3b was determined using X-ray crystallography. The cytotoxicity of complexes against ovarian (A2780, SK-OV-3) and breast (MDA-MB-231) cancer cell lines and noncancerous cell line HEK-293 was evaluated and compared to cisplatin activity. The carbohydrate-modified complexes bearing acyl-protecting groups exhibited higher efficacy (in low micromolar range) than unprotected ones, where the most active 4d was superior to cisplatin up to five times against all investigated cancer cell lines; however, no significant selectivity was achieved. The complex induced apoptotic cell death at low micromolar concentrations (0.5 μM for A2780 and HEK293; 2 μM for SK-OV-3 and MDA-MB-231).  相似文献   

9.
A new unsymmetrical five-coordinate Schiff base ligand (HL) with an N4O donor set ( 2 ) has been prepared by condensation of N1-(2-morpholinoethyl)-N1-([pyridine-2-yl]methyl)propane-1,3-diamine with 2-hydroxy-benzaldehyde. Metal complexes [ML]n+ (M = Zn2+, Cd2+, Mn2+, Cu2+, Ni2+, Ag+, Fe3+, and Co2+ ( 3–10 ) were synthesized by the reaction of the ligand and metal salts in ethanol. The resulting products were characterized by elemental analyses, infrared, 1H and 13C nuclear magnetic resonance spectra (in the case of Cd and Zn complexes), UV–Vis, electrospray ionization-mass spectrometric, and conductivity measurements. The structure of the complexes [ZnL](ClO4) ( 3 ), [CdL](ClO4) ( 4 ), and [CuL](ClO4) ( 7 ) has been determined by single-crystal X-ray diffraction analysis. The metal complexes were determined to have a distorted trigonal bipyramidal (Zn and Cd) or a distorted square pyramidal (Cu) geometry. The cytotoxic potential of each compound (1–10) against MCF-7 and MDA-MB-231 (breast cancer cells), PC-3 (prostate cancer cells), and WI-38 human normal lung fibroblast cells was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Compounds 1, 2, and 10 did not display any activity toward any cell line tested. None of the compounds except compound 8 was cytotoxic toward PC-3. Compounds 4 and 8 showed the highest cytotoxic activity against the MCF-7 and MDA-MB-231 cell lines. Because compounds 3, 6, and 9 have similar half-maximal inhibitory concentration values against cancer cells and normal cells, these compounds displayed poor selectivity between cancer and normal cells. More importantly, it was observed that compound 5 acts differently toward different types of cell lines. For example, it displays lower cytotoxicity against the WI-38 normal cell line than it does against the MDA-MB-231 cell line.  相似文献   

10.
We designed and synthesized the 1,3,4-thiadiazole derivatives differing in the structure of the substituents in C2 and C5 positions. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and normal cell line (fibroblasts). The results showed that in both breast cancer cell lines, the strongest anti-proliferative activity was exerted by 2-(2-trifluorometylophenylamino)-5-(3-methoxyphenyl)-1,3,4-thiadiazole. The IC50 values of this compound against MCF-7 and MDA-MB-231 breast cancer cells were 49.6 µM and 53.4 µM, respectively. Importantly, all new compounds had weaker cytotoxic activity on normal cell line than on breast cancer cell lines. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds. The most likely mechanism of action for the new compounds is connected with the activities of Caspase 3 and Caspase 8 and activation of BAX proteins.  相似文献   

11.
A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates 2a–2h were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-b]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines—MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated. The results demonstrated that three compounds caused growth inhibition in both TNBC cell lines, with little or no effect against the non-tumorigenic cells. The most promising compound was further studied concerning possible effects on cell viability (by trypan blue exclusion assay), cell proliferation (by bromodeoxyuridine assay) and cell cycle profile (by flow cytometry). The results demonstrated that the GI50 concentration of compound 2e (13 μM) caused a decreased in MDA-MB-231 cell number, which was correlated with a decreased in the % of proliferating cells. Moreover, this compound increased G0/G1 phase and decreased S phases, when compared to control cells (although was not statistic significant). Interestingly, compound 2e also reduced tumor size using an in ovo CAM (chick chorioallantoic membrane) model. This work highlights the potential antitumor effect of a novel methyl 3-arylthieno[3,2-b]pyridine-2-carboxylate derivative.  相似文献   

12.
A number of 2,3-diarylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of six cancer cell lines including human hepatocellular carcinoma (Hep G2 and Hep 3B), non-small cell lung cancer (A549 and H1299), and breast cancer (MCF-7 and MDA-MB-231) cell lines. The preliminary results indicated that 6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline (16b) was one of the most active compounds against the growth of Hep 3B, H1299, and MDA-MB-231 with a GI(50) value of 0.71, 1.46, and 0.72 μM respectively which was more active than tamoxifen. Further investigations have shown that 16b induced cell cycle arrest at G2/M phase followed by DNA fragmentation via an increase in the protein expression of Bad, Bax and decrease in Bcl-2, and PARP which consequently cause cell death.  相似文献   

13.
Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.  相似文献   

14.
The synthesis of optically active trinorditerpenes was carried out, and their antimicrobial and antitumor activity was tested. The synthetic derivative 12-hydroxypodocarpa-8,11,13-triene (7) showed GI50 at 6.6 µM against breast cancer MDA-MB-435 (LC50 = 50.9 µM and log10 GI50 = −5.18). The 12-acetyloxypodocarpa-8,11,13-triene (8) showed GI50 at 12.1 µM against leukemia RPMI-8226 (LC50 = 76.1 µM and log10GI50 = −4.92).__________Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 255–259, May–June, 2005.  相似文献   

15.
B- and c-series of gangliosides are over-expressed in neuro-ectoderm-related cancers, including breast cancer. It has been shown that GD3 ganglioside is over-expressed in about 50% of invasive ductal breast carcinoma and the GD3 synthase (GD3S) gene displays higher expression among estrogen receptor (ER) negative breast tumors. We previously showed that GD3S expression in MDA-MB-231 breast cancer cells induces the expression of GD2 and increased cell proliferation and migration via a GD2-dependent activation of c-Met receptor. Here, we show that in ER-positive MCF-7 breast cancer cells, GD3S expression resulted in an increase of GD1b, which was associated with a decrease of GM1a and GM2. Meanwhile, GD3S expressing MCF-7 cells exhibited an increased migration without any modification of proliferation rate. Therefore, GD3S expression can result in different modifications of both ganglioside profiles and cell phenotypes depending on breast cell types.  相似文献   

16.
Abstract

Gypensapogenin H (Gyp H) is a novel dammarane-type triterpene, isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that Gyp H exhibited potent growth inhibitory effects on tumor cells. It significantly inhibited the growth of human breast cancer cells (MDA-MB-231), while having low toxicity to normal human breast epithelial cells, MCF-10a. Further mechanistic study demonstrated that Gyp H decreased survival, inhibited proliferation, migration, induced apoptosis and led to cell cycle arrest. For the MDA-MB-231 cell lines, Gyp H increased expression of P21, Bax and cytochrome c, induced PARP cleavage and activated caspases. Gyp H also reduced expression of CDK2/4, CyclinD1, E2F1 and Bcl2, which associated with the cell cycle arrest. Thus, our finding may be useful for understanding the mechanism of action of Gyp H on breast cancer cells and suggest that Gyp H would be a leading agent for the treatment of breast cancer.  相似文献   

17.
A number of tri- and hexaosmium carbonyl cluster derivatives were screened for cytotoxicity against five cancer cell lines, and the hexaosmium carbonyl clusters Os6(CO)18 and Os6(CO)16(NCCH3)2 were found to be active against four of these, viz., ER+ breast carcinoma (MCF-7), ER-breast carcinoma (MDA-MB-231), metastatic colorectal adenocarcinoma (SW620) and hepatocarcinoma (Hepg2), with IC50 values as low as 6 μM. Studies on their mode of action with the MDA-MB-231 cell line pointed to the induction of apoptosis, as has been found earlier for the trinuclear cluster Os3(CO)10(NCCH3)2.  相似文献   

18.
Three series of artemisinin-isatin hybrids 8a-i, 10a-c and 11a-e were designed, synthesized and evaluated for their antiproliferative activity against breast cancer cells (MCF-7, MDA-MB-231 and doxorubicin-resistant MCF-7 (MCF-7/DOX)), as well as the cytotoxicity towards normal MCF-10A breast cells. The preliminary results showed that a significant part of the synthesized hybrids (IC50: 20.7–99.9 µM) were active against both drug-sensitive and doxorubicin-resistant breast cancer cell lines. The structure–activity relationship illustrated that the linker between artemisinin and isatin moieties as well as the substituents on C-3 and C-5 position of isatin motif had great influence on the activity. In particular, hybrids 11c,d were found to be most active against all tested breast cancer cell lines, and their activity was not inferior to that of doxorubicin. Therefore, hybrids 11c,d could serve as useful templates for the development of novel anti-breast cancer agents.  相似文献   

19.
A library of acetamide and hydrazine analogues were generated on the pyrimidine ring through a multistep reaction starting from 5-nitro-pyrimidine-4,6-diol and pyrimidine-4,6-diol, respectively. The synthesized analogues were screened for in vitro cytotoxic activity against various human cancer cell lines like HCT-1 and HT-15 (colon), MCF-7(breast), PC-3 (prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though many of the synthesized derivatives exhibited a good potency against various screened cancer cell lines, compound 14a from the acetamide series was found to show potent anticancer activity on all the tested cancer cell lines with IC50 value of 0.36μM on CNS cell line and 1.6μM on HT-21 cell line, and compound 19xxi from hydrazine series of pyrimidine showed potent activity against three tested cancer cell lines with IC50 value of 0.76μM on HT-29 cell line, 2.6μM on HCT-15, and 3.2μM on MCF-7 cell line.  相似文献   

20.
Chemical composition, antioxidant, anticancer, and antimacrobial activities of essential oil obtained from leaves of Rumex nervosus has been evaluated here for the first time. GC/MS analysis reveals the presence of Palmitoleic Acid (28.35%) and Palmitic acid, (25. 37%) as their methyl ester as major components. The essential oil showed significant DPPH radical scavenging activity (94.907 ± 0.1089% and 94.003 ± 0.0749%) at concentration (100 and 80) μg/mL respectively. The oil showed promising activity against staph aureus, while showed weak activity against (Hela and 3T3) cell lines. The crude extract / fractions of R. nervosus (leaves) showed significant antioxidant activity at dose (100 and 80) μg/mL. Futhermore the crude showed significant activity against (MCF-7 and MDA-MB-231) cell lines with IC50 (20.5138 ± 0.933 and 25.1728 ± 0.9176) μg/mL respectively, and chloroform fraction showed good activity against (MCF-7 and MDA-MB-231) cell lines with IC50 (31.154 ± 0.965 and 42.269 ± 2.1045) μg/mL.  相似文献   

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