Platinum(ii) clovers targeting G-quadruplexes and their anticancer activities

2015 ◽  
Vol 44 (1) ◽  
pp. 50-53 ◽  
Author(s):  
Xiao-Hui Zheng ◽  
Qian Cao ◽  
Yi-Liang Ding ◽  
Yi-Fang Zhong ◽  
Ge Mu ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Telomerase Activity ◽  
Anticancer Activities ◽  
Dual Effect ◽  
Oncogene Expression

The excellent anticancer activity of platinum(ii) clovers is the result of a dual effect, inhibition of the telomerase activity and repression of oncogene expression.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

scholarly journals Increases of Lipophilic Antioxidants and Anticancer Activity of Coix Seed Fermented by Monascus purpureus

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Haiying Zeng ◽  
Likang Qin ◽  
Xiaoyan Liu ◽  
Song Miao
Keyword(s):  
Anticancer Activity ◽  
Radical Scavenging ◽  
Monascus Purpureus ◽  
Acid Oxidation ◽  
Anticancer Activities ◽  
Lipophilic Extract ◽  
Coix Seed ◽  
Before And After ◽  
Health Promoting ◽  
Human Laryngeal Carcinoma

Lipophilic tocols, γ-oryzanol, and coixenolide in coix seed before and after fermentation by Monascus purpureus were determined. Antioxidant and anticancer activities of raw and fermented coix seed were evaluated using free-radical-scavenging assays and polyunsaturated fatty acid oxidation model, and human laryngeal carcinoma cell HEp2, respectively. Compared to the raw seed, the tocols, γ-oryzanol, and coixenolide contents increased approximately 4, 25, and 2 times, respectively, in the fermented coix seed. Especially, γ-tocotrienol and γ-oryzanol reached 72.5 and 655.0 μg/g in the fermented coix seed. The lipophilic extract from fermented coix seed exhibited higher antioxidant activity in scavenging free radicals and inhibiting lipid oxidation. The inhibitory concentrations for 50% cell survival (IC50) of lipophilic extract from fermented coix seed in inhibiting HEp2 cells decreased by 42%. This study showed that coix seed fermented by M. purpureus increased free and readily bioavailable lipophilic antioxidants and anticancer activity. Therefore, fermentation could enhance the efficacy of the health promoting function of coix seeds.

scholarly journals NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Anticancer Activities ◽  
Gene Expressions

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.

Synthesis, optical properties, and antioxidant and anticancer activity of benzoheterazole dendrimers with triazole bridging unit

2018 ◽  
Vol 42 (5) ◽  
pp. 3282-3292 ◽  
Author(s):  
Kannan Rajavelu ◽  
Mamangam Subaraja ◽  
Perumal Rajakumar
Keyword(s):  
Optical Properties ◽  
Bisphenol A ◽  
Anticancer Activity ◽  
Click Chemistry ◽  
Anticancer Activities

Benzoheterazole dendrimers with triazole bridges and bisphenol A/benzophenone core units have been successfully synthesized by click chemistry. Higher generation dendrimers exhibit better antioxidant and anticancer activities than the lower generation dendrimers.

Anticancer Activity and High Content Screening of New 6-Substituted-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazoline Derivatives

2021 ◽  
pp. 2397-2405
Author(s):  
Hiba Ali Hasan ◽  
Afrah Salman ◽  
Abdulmalek Emilia
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Elemental Analysis ◽  
Inhibitory Concentration ◽  
High Content Screening ◽  
Spectroscopic Methods ◽  
High Toxicity ◽  
Anticancer Activities ◽  
Microwave Assisted ◽  
Quinazoline Derivatives

Pursuing our interest in bioactive heterocyclic compound, two benzoimidazoquinazoline derivatives were synthesised using both microwave-assisted and classical heating methods. Structures of the compounds were confirmed by standard spectroscopic methods and elemental analysis. The target scaffolds were incidentally found to emit blue light when exposed to ultraviolet light. Consequently, a photoluminescence characterization was carried out as a part of characterization protocol. The anticancer activities of the benzimidazoquinazoline compounds were investigated using both methylthiazol tetrazolium (MTT) and the high content screen (HCS) assays against liver hepatocellular cells. The results showed a significant reduction in the inhibitory concentration of the cancer cells by 1 and 2.6 fold when exposed to compounds (3a) and (3b), respectively. The high content screen (HCS) was conducted for compound (3b) and the results showed high toxicity towards the cancer cells.

scholarly journals Pyrrolizine-5-carboxamides: Exploring the impact of various substituents on anti-inflammatory and anticancer activities

2018 ◽  
Vol 68 (3) ◽  
pp. 251-273 ◽  
Author(s):  
Ahmed M. Gouda ◽  
Ahmed H. Abdelazeem ◽  
Ashraf N. Abdalla ◽  
Muhammad Ahmed
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Inflammatory Activity ◽  
Electronic Effects ◽  
Anticancer Activities ◽  
Phenyl Rings ◽  
Anti Inflammatory ◽  
New Compounds ◽  
The Impact ◽  
Mcf 7

Abstract Towards optimization of the pyrrolizine-5-carboxamide scaffold, a novel series of six derivatives (4a-c and 5a-c) was prepared and evaluated for their anti-inflammatory, analgesic and anticancer activities. The (EZ)-7-cyano-6-((4-hydroxybenzylidene)amino)-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4b) and (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5b) bearing the electron donating methyl group showed the highest anti-inflammatory activity while (EZ)-6-((4-chlorobenzylidene)amino)-7-cyano-N-phenyl-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5a) was the most active analgesic agent. Cytotoxicity of the new compounds was evaluated against the MCF-7, A2780 and HT29 cancer cell lines using the MTT assay. Compounds 4b and 5b displayed high anticancer activity with IC50 in the range of 0.30–0.92 μmol L−1 against the three cell lines, while compound (EZ)-N-(4-chlorophenyl)-7-cyano-6-((4-hydroxybenzylidene)-amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4c) was the most active against MCF-7 cells (IC50 = 0.08 μmol L−1). Both the anti-inflammatory and anticancer activities of the new compounds were dependent on the type of substituent on the phenyl rings. Substituents with opposite electronic effects on the two phenyl rings are preferable for high cytotoxicity against the MCF-7 and A2780 cells. COX inhibition was suggested as the molecular mechanism of the anti-inflammatory activity of the new compounds while no clear relationship could be observed between COX inhibition and anticancer activity. Compound 5b, the most active against the three cell lines, induced dose-dependent early apoptosis with 0.1–0.2 % necrosis in MCF-7 cells. New compounds showed promising drug-likeness scores while the docking study revealed high binding affinity to COX-2. Taken together, this study highlighted the significant impact of the substituents on the anti-inflammatory and anticancer activity of pyrrolizine-5-carboxamides, which could help in further optimization to discover good leads for the treatment of cancer and inflammation.

scholarly journals Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 191
Author(s):  
Ambre Dezaire ◽  
Christophe H. Marchand ◽  
Marine Vallet ◽  
Nathalie Ferrand ◽  
Soraya Chaouch ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Crude Extract ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Chemical Library ◽  
Altered Expression ◽  
Cancer Aggressiveness

High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.

Structural requirements of salicylaldehyde benzoylhydrazones and their Cu(II) complexes for anticancer activity

2012 ◽  
Vol 90 (9) ◽  
pp. 762-775 ◽  
Author(s):  
Shiow Jin Tan ◽  
Mahasin Alam Sk ◽  
Peter Peng Foo Lee ◽  
Yaw Kai Yan ◽  
Kok Hwa Lim
Keyword(s):  
Anticancer Activity ◽  
Density Functional ◽  
Chemical Potential ◽  
Biological Activities ◽  
Principal Component Regression ◽  
Principal Component ◽  
Atomic Charges ◽  
Anticancer Activities ◽  
Structural Requirements ◽  
Qsar Analysis

Salicylaldehyde benzoylhydrazone (H2sb) has a variety of biological activities including anticancer activity. The Cu(II) complexes of H2sbs possess enhanced anticancer activity as compared with their free ligands. A quantitative structure–activity relationship (QSAR) analysis was performed on a series of H2sb ligands and their corresponding Cu(II) complexes to capture the structural requirements that are responsible for the bioactivity. The predictive QSAR models were developed using statistical techniques such as multiple linear regression (MLR) and principal component regression analysis (PCRA). We used different combinations of various descriptors such as a physicochemical descriptor, electrotopological state atom (ETSA) indices, and descriptors derived from density functional theory (DFT) calculations. The DFT-derived descriptors used for QSAR analysis are HOMO and LUMO energies, atomic charges, chemical potential, and hardness. Our developed models showed the importance of the lipophilicity index (ClogP), ETSA indices, and atomic charges for anticancer activities of the H2sb analogs and their Cu(II) complexes. In addition, our MLR models revealed that, while the global lipophilicity index and hardness are important for anticancer activity of H2sb ligands, chemical potential and HOMO energy are important for the anticancer activity of Cu(II) complexes.

3D-QSAR STUDIES OF SUBSTITUTED 4-ARYL/HETEROARYL-4H-CHROMENES AS APOPTOSIS INDUCERS USING CoMFA AND CoMSIA

2009 ◽  
Vol 08 (01) ◽  
pp. 143-155 ◽  
Author(s):  
SI YAN LIAO ◽  
LI QIAN ◽  
TI FANG MIAO ◽  
YONG SHEN ◽  
KANG CHENG ZHENG
Keyword(s):  
Anticancer Activity ◽  
Predictive Ability ◽  
Decisive Role ◽  
3D Qsar ◽  
Field Analysis ◽  
Breast Cancer Cell Lines ◽  
Steric Interaction ◽  
Anticancer Activities ◽  
Strong Electron ◽  
Qsar Studies

Three-dimensional (3D) quantitative structure–activity relationships (QSARs) of 36 apoptosis inducers, substituted 4-aryl/heteroaryl-4H-chromenes with anticancer activity against human breast cancer cell lines T47D, have been studied by using methods of comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA). The established 3D-QSAR models in training set show not only significant statistical quality, but also predictive ability, with high correlation coefficient (R2) values and cross-validation coefficient (q2) values: CoMFA (R2, q2: 0.944, 0.747), CoMSIA (R2, q2: 0.944, 0.704). Moreover, the predictive abilities of the CoMFA and CoMSIA models were further confirmed by a test set, giving the predictive correlation coefficients ([Formula: see text] values) of 0.845 and 0.851, respectively. Based on the CoMFA and CoMSIA contour map analyses, some key factors responsible for anticancer activity of this series of compounds have been found as follows: the steric interaction plays a decisive role in determining the anticancer activities of these compounds; bulky groups as substituent R 1 are not tolerated; in addition to a steric moderation, higher degree of electropositivity and hydrophobicity on the terminal alkyl of substituent R 2 might be favorable to the activity; the substituent R 3 should be hydrophobic; bulky and strong electron withdrawing groups for the substituent R 4 are not advantageous to the activity; simultaneously introducing large electronegative atoms as hydrogen-acceptors to the first atoms of the substituents R 5 and R 6 may increase the activity, but substituents R 5 and R 6 with a linking group – OCH 2 O – may decrease the activity. Such results can offer some useful theoretical references for understanding the action mechanism, designing more potent derivatives, and predicting their activities prior to synthesis.

Sign in / Sign up

Export Citation Format

Share Document