scholarly journals DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xiao-mei Mo ◽  
Zhan-fang Chen ◽  
Xin Qi ◽  
Yan-tuan Li ◽  
Jing Li
Keyword(s):  
Dna Binding ◽  
Anticancer Agents ◽  
Topoisomerase I ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Vanadium Compound ◽  
New Class ◽  
M Phase ◽  
Low Toxicity ◽  
Topo Ii

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal anticancer agents in combination to its low toxicity. Here, we found a vanadium compound Van-7 as an inhibitor of Topo I other than Topo II using topoisomerase-mediated supercoiled DNA relaxation assay. Agarose gel electrophoresis and comet assay showed that Van-7 treatment did not produce cleavable complexes like HCPT, thereby suggesting that Topo I inhibition occurred upstream of the relegation step. Further studies revealed that Van-7 inhibited Topo I DNA binding involved in its intercalating DNA. Van-7 did not affect the catalytic activity of DNase I even up to100 μM. Van-7 significantly suppressed the growth of cancer cell lines with IC50at nanomolar concentrations and arrested cell cycle of A549 cells at G2/M phase. All these results indicate that Van-7 is a potential selective Topo I inhibitor with anticancer activities as a kind of Topo I suppressor, not Topo I poison.

S16020 pyridocarbazole derivatives display high activity to lung cancer cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Gabriela Chabowska ◽  
Helena Moreira ◽  
Beata Tylińska ◽  
Ewa Barg
Keyword(s):  
Cell Viability ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Wide Spectrum ◽  
A549 Cells ◽  
Biological Evaluation ◽  
Dna Intercalation ◽  
P Glycoprotein ◽  
Low Toxicity ◽  
And Migration

Background: Despite the dynamic development of medicine, globally cancer diseases remain the second leading cause of death. Therefore, there is a strong necessity to improve chemotherapy regimens and search for new anticancer agents. Pyridocarbazoles are compounds with confirmed antitumor properties based on multimodal mechanisms, i.a. DNA intercalation and topoisomerase II-DNA complex inhibition. One of them, S16020, displayed a wide spectrum of activity. Objective: The aim of the study was to investigate the antitumor potency of six S16020 derivatives, synthesized according to the SAR (structure-activity relationship) method. Methods: The biological evaluation included influence on cancer cell viability, proliferation, and migration, as well as P-glycoprotein activity. NHDF, A549, MCF-7, LoVo, and LoVo/DX cell lines were used in the study. Results: All derivatives displayed low toxicity to normal (NHDF) cells at 1 and 2 µM (≤ 20% of cell growth inhibition). The highest reduction in cell viability was noted in A549 cells which was accompanied by significant disruption of cells proliferation and motility. Compound 1 exhibited the strongest cytotoxic, antiproliferative, and antimigratory effects, higher than the reference olivacine. A significant reduction in P-glycoprotein activity was found for derivatives 6 and 1. Conclusion: S16020 derivatives could be considered as potential candidates for new anticancer drugs.

scholarly journals Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 437
Author(s):  
Shu-Qin Qin ◽  
Lian-Chun Li ◽  
Jing-Ru Song ◽  
Hai-Yun Li ◽  
Dian-Peng Li
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

scholarly journals Identification and Validation of Novel Microtubule Suppressors with an Imidazopyridine Scaffold through Structure Based Virtual Screening and Docking.

2021 ◽  
Author(s):  
Samia A Elseginy ◽  
A Sofia F Oliveira ◽  
Deborah K Shoemark ◽  
Richard B Sessions
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
3D Structure ◽  
Cancer Cell Proliferation ◽  
Cycle Arrest ◽  
Colchicine Binding Site ◽  
Apoptotic Protein ◽  
M Phase ◽  
Low Toxicity

Targeting the colchicine binding site of alpha/beta tubulin microtubules can lead to suppression of microtubule dynamics, cell cycle arrest and apoptosis. Therefore, development of microtubule (MT) inhibitors is considered a promising route to anticancer agents. Our approach to identify novel scaffolds as MT inhibitors depends on a 3D-structure based pharmacophore approach and docking using three programmes MOE, Autodock and BUDE (Bristol University Docking Engine) to screen a library of virtual compounds. From this work we identified the compound 7-(3-Hydroxy-4-methoxy-phenyl)-3-(3-trifluoromethyl-phenyl)-6,7-dihydro-3H-imidazo[4,5-b] pyridin-5-ol (6) as a novel inhibitor scaffold. This compound inhibited several types of cancer cell proliferation at low micromolar concentrations with low toxicity. Compound 6 caused cell cycle arrest in the G2/M phase and blocked tubulin polymerization at low micromolar concentration (IC50 = 6 micromolar, inducing apoptosis via activation of caspase 9, increasing the level of the pro-apoptotic protein Bax and decreasing the level of the anti-apoptotic protein Bcl2. In summary, our approach identified a lead compound with potential antimitotic and antiproliferative activity.

Spectroscopic and In Silico DNA Binding Studies on the Interaction of Some New N-Substituted Rhodanines with Calf-thymus DNA: In Vitro Anticancer Activities

2019 ◽  
Vol 19 (3) ◽  
pp. 425-433 ◽  
Author(s):  
Imran Ali ◽  
Mohammad N. Lone ◽  
Zeid A. Alothman ◽  
Ahmad Y. Badjah ◽  
Abdullah G. Alanazi
Keyword(s):  
Dna Binding ◽  
Anticancer Agents ◽  
In Silico ◽  
Calf Thymus Dna ◽  
Black Dot ◽  
Anticancer Activities ◽  
Binding Studies ◽  
Molecular Docking Study ◽  
Calf Thymus ◽  
Dna Binding Studies

Background: In this era of science, cancer is a black dot on the face of humankind. Consequently, the search of promising anticancer agents continues. Aims: Here we designed and synthesized new N-substituted rhodanines (RD1-7), evaluated their multispectroscopic interaction with calf thymus DNA, in silico and anticancer studies against MDA-MB-231cancer cell line. Methods: By MTT assay rhodanine RD1 was found to be the most potent with IC50 value of 72.61 μM. In addition, DNA binding studies (UV-vis and fluorescence) revealed strong binding affinity of RD1-7 with DNA (Kb in the range of 1.5-7.4 × 105 M-1). Moreover, molecular docking study, experimental DNA binding and anticancer studies are all well agreed to each other. Results: It was observed that H-bonding and hydrophobic attractions were responsible for stability of DNAcompound adducts. Besides, the reported rhodanines (RD1-7) were found as minor groove binders of DNA. Concisely, RD1-7 indicated promising pharmacological properties and hence, shows auspicious future for the development of novel anticancer agents. Conclusion: The reported rhodanines showed excellent anticancer properties. Therefore, the described rhodanines may be used as potential anticancer agents in the future.

Two New Oxovanadium(IV) Compounds Containing Amino Acid Schiff Base and 1,10-Bathophenanthroline Ligands: Syntheses, Crystal Structures, and In Vitro Evaluation of the Anticancer Activities

2017 ◽  
Vol 70 (5) ◽  
pp. 608 ◽  
Author(s):  
Yaping Cao ◽  
Hongmei Liu ◽  
Zeli Yuan ◽  
Gang Wei
Keyword(s):  
Schiff Base ◽  
Anticancer Agents ◽  
High Resolution Mass Spectrometry ◽  
Hepatoma Cell ◽  
A549 Cells ◽  
Molar Conductance ◽  
Anticancer Activities ◽  
Human Hepatoma Cell ◽  
Ic50 Values

Two new oxovanadium(iv) compounds containing 1,10-bathophenanthroline (Bphen) and amino Schiff base derivatives [VO(hnd-napha)(Bphen)] (1) and [VO(o-van-met)(Bphen)] (2) were synthesised (where hnd-napha and o-van-met are N-Schiff bases derived from the reaction of 2-hydroxy-1-naphthaldehyde with 3-(1-naphthyl)-l-alanine and o-vanillin with l-methionine, respectively). These compounds were characterised by elemental analysis, infrared spectroscopy, high-resolution mass spectrometry, and single-crystal X-ray diffraction (XRD). Both compounds showed low molar conductance values, indicating that they are non-electrolytes. The XRD results showed that the VIV atoms in both compounds existed in the VO3N3 coordination geometry with Schiff base and Bphen ligands. The in vitro anticancer activities of compounds 1 and 2 were evaluated against A549 human lung carcinoma and HepG2 human hepatoma cell lines using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results revealed that both compounds were cytotoxic with half maximal inhibitory concentration (IC50) values in the range of 8.22 ± 1.0 to 94.89 ± 3.2 μmol L−1. Notably, compound 2 exhibited much better anticancer activity in vitro against A549 cells (8.22 ± 1 μmol L−1) than [VO(acac)2] (24 ± 6 μmol L−1) or any of our previously reported oxovanadium(iv) compounds, making it comparable in activity to cisplatin (3.1 ± 0.5 μmol L−1). These results therefore suggest that compound 2 could be used as a promising lead for the development of anticancer agents for the treatment of lung cancer.

Recent Developments in Anticancer Activity of Compounds Containing the Thioether Group

2020 ◽  
Vol 20 ◽  
Author(s):  
Muhammad İ. Han ◽  
Şükriye G. Küçükgüzel
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Research Field ◽  
Cancer Development ◽  
Anticancer Activities ◽  
Cancer Disease ◽  
New Class ◽  
Research Activities ◽  
Recent Developments ◽  
Patent Literature

Background: Spreading rapidly in recent years, cancer has become the cause of one of the highest mortality rates after cardiovascular diseases. With more attention being directed to cancer, anticancer research has become an important research field. In spite of enormous research activities in this area, the reason for cancer development is still not clearly understood. Scientists are now working on the biology of cancer, especially on the root of the cause for cancer development. The aim is to treat the cancer disease, and thus cure the patients. Continuing efforts on the development of novel molecules as potential anticancer agents is essential for this purpose. Objective: The main aim of this review was to present a survey on the medicinal chemistry of thioethers and to provide practical data on their cytotoxicities against various cancer cell lines. Methods: Research articles published between 2001-2019 were consulted in the preparation of this review article though patent literature was not included here. Results: Compounds containing thioether functionality were proven to have anticancer activities. Indeed, thioether functionality was found to be a must in some cases to show anticancer activity. Conclusion: Thioether containing molecules may emerge as new class of potent and effective anticancer agents in the near future.

scholarly journals 12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway

2020 ◽  
Vol 21 (20) ◽  
pp. 7579
Author(s):  
Ju-Ying Tsai ◽  
Dóra Rédei ◽  
Judit Hohmann ◽  
Chin-Chung Wu
Keyword(s):  
Lung Cancer ◽  
Anticancer Agents ◽  
Cell Cycle Progression ◽  
Nuclear Translocation ◽  
Growth Arrest ◽  
A549 Cells ◽  
Cell Types ◽  
Human Lung Cancer ◽  
M Phase ◽  
Induced Apoptosis

Prostratin, a non-tumor promoting 12-deoxyphorbol ester, has been reported as a protein kinase C (PKC) activator and is shown to have anti-proliferative activity in certain cancer cell types. Here we show that GRC-2, a prostratin analogue isolated from Euphorbia grandicornis, is ten-fold more potent than prostratin for inhibiting the growth of human non-small cell lung cancer (NSCLC) A549 cells. Flow cytometry assay revealed that GRC-2 and prostratin inhibited cell cycle progression at the G2/M phase and induced apoptosis. The cytotoxic effect of GRC-2 and prostratin was accompanied by activation and nuclear translocation of PKC-δ and PKD as well as hyperactivation of extracellular signal-related kinase (ERK). Knockdown of either PKC-δ, PKD or ERK significantly protected A549 cancer cells from GRC-2- and prostratin-induced growth arrest as well as apoptosis. Taken together, our results have shown that prostratin and a more potent analogue GRC-2 reduce cell viability in NSCLC A549 cells, at least in part, through activation of the PKC-δ/PKD/ERK pathway, suggesting the potential of prostratin and GRC-2 as anticancer agents.

Evaluation of Cytotoxic Potentials of Some Isoindole-1, 3-Dione Derivatives on HeLa, C6 and A549 Cancer Cell Lines

2020 ◽  
Vol 16 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Ayse Tan ◽  
Ayse Sahin Yaglioglu ◽  
Nurhan Horasan Kishali ◽  
Ertan Sahin ◽  
Yunus Kara
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
In Vivo Studies ◽  
Silyl Ether ◽  
Anticancer Activities ◽  
Alkyl Aryl ◽  
Starting Compound

Objective: Considering this information, firstly, isoindole derivatives containing different functional groups 4-13 have been synthesized from 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole-1, 3(2H)-dione. Background: Norcantharimides are known as norcantharidine derivatives and contain an isoindole skeleton structure. Isoindole derivatives have positive effect on inflammatory pathologies including cancers. Methods: For the synthesis of all compounds, 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole- 1,3(2H)-dione was used as the starting compound. The syntheses were based on two main reactions: Ene-reaction of singlet oxygen and epoxidation. Secondly, their anticancer activities were evaluated against HeLa, C6 and A549 cancer cell lines by the BrdU assay. Results: Anticancer activities of synthesized compounds (4-13) and 5-FU (5-Florouracil) against HeLa, C6 and A549 cells were investigated at four concentrations (100, 50, 25 and 5 μM). IC50 values of compounds 4-13 were calculated for all cancer cell lines. The investigated compounds showed anticancer activity against the cancer cell lines depending on doses. Compound 7 containing azide and silyl ether exhibited higher inhibitory activity than the other compounds and 5-FU against A549 cancer cell lines (IC50 =19.41± 0.01 μM). Compounds 9 and 11 were determined to exhibit cell-selective activity against HeLa cancer cell lines. Compound 11 had higher activity than the positive control at 100 μM concentrations against C6 cancer cell lines. Conclusion: According to the results observed, isoindole derivatives 7, 9, and 11 might be good potential anticancer agents for the treatment of cervical and glioma cancer due to their antiproliferative properties, having less cytotoxic effects on healthy cells. In addition, compound 7 could be used in in vivo studies of all three-cancer cell lines (C6, HeLa, and A549).

Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity via Tubulin Inhibition

2020 ◽  
Vol 20 (12) ◽  
pp. 1469-1474
Author(s):  
Lavanya Reddy ◽  
Suja T. Dharmabalan ◽  
Kanakaraju Manupati ◽  
Ragini Yeeravalli ◽  
Lakshmi D. Vijay ◽  
...  
Keyword(s):  
Small Molecules ◽  
Anticancer Agents ◽  
Tubulin Polymerization ◽  
Molecular Binding ◽  
New Class ◽  
Ic50 Value ◽  
Tubulin Binding ◽  
M Phase ◽  
Mcf 7 ◽  
Coupling Sequence

Background: Discovery of small molecules that inhibit tubulin polymerization is an attractive strategy for the development of new and improved anti-proliferative agents. Objective: A series of novel 2-sulfonyl-1,1-diarylethenes were designed towards this end keeping in view the favorable chemical and pharmacological virtues of unsaturated sulfones. Methods: Rapid, convenient and efficient two-step assembly of the designed molecules was achieved by the vicinal iodo-sulfonylation-Suzuki coupling sequence. Results: As hypothesized, these compounds showed good anti-proliferative activity against different tissuespecific cancer cell lines: MCF-7, DU-145, A-549, HepG2, and HeLa. The most active compound, pnitrophenyl ring-bearing analog, exhibited an IC50 value of 0.90μM against A-549 cells. Flow cytometry studies on this derivative revealed that it arrests the cell cycle of A-549 cells at the G2/M phase. This compound exhibited molecular binding to tubulin as well as tubulin polymerization inhibition comparable to that of colchicine. Conclusion: A new class of potent, tubulin binding anticancer agents based on 1,1,-diarylvinyl sulfone scaffold has been designed and synthesized.

Synthesis and Biological Evaluation of New 1,2,3-Triazole Derivatives of the Chrysin Flavonoid as Anticancer Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Venkatagiri Noole ◽  
Thotla Krishna ◽  
Sudhakar Godeshala ◽  
Seyedehmelika Meraji ◽  
Kaushal Rege ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
13C Nmr Spectroscopy ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Ic50 Value ◽  
M Phase ◽  
Pc3 Cells ◽  
Ft Ir ◽  
Mcf 7

Background and Objective: Chrysin and its derivatives proved to possess potential anti-tumour activity. Materials and Methods: A new series of chrysin analogs containing 1,2,3-triazoles with different substituent groups (5a-5l) was designed, synthesized, and evaluated as potential anticancer agents. The synthesized compounds were characterized using FT-IR, 1H NMR 13C NMR spectroscopy and mass spectrometry. Resulsts: The anticancer activities of the synthesized compounds were studied in four cancer cell lines viz.PC3, PC3-PSMA, MCF-7 and UM-UC-3 using doxorubicin as standard. Among all the tested compounds 5c was found as most active with IC50 value of 10.8 ± 0.04 µM in PC3 cells and 20.53 ± 0.21 µMin MCF-7 cells respectively. Flow cytometry analyses indicated that synthesized compounds 5a,5c and 5h arrested MCF-7 cells at the G2/M phase in a dose-dependent manner. Conclusion: Chyrsin derivatives could be novel anticancer agents.

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