Synthesis, Cytotoxicity, Anti-migration and Anti-invasion Activity of Diphyllin Heterocyclic Derivatives

Background: Diphyllin, an arylnaphthalene lignan lactone, isolated from many traditional medicinal plants, has been reported to possess anticancer and antiviral activities. Natural diphyllin and its glycosides were identified as potent vacuolar H+ -ATPase (V-ATPase) inhibitors. Objective: The aim of this study was to design and synthesize a series of heterocyclic derivatives of diphyllin as novel anticancer agents. Methods: The targeted heterocyclic derivatives of diphyllin were synthesized from diphyllin employing etherification reaction and N-substitution reaction. Cytotoxicity of these compounds on four cancer cells was assessed by MTT assay. The inhibitory activity of V-ATPase of compound 3n was measured on MGC-803 cells. Anti-migration and anti-invasion abilities were assessed by transwell invasion assay and scratch wound assay. Results: Most of these derivatives displayed potent cytotoxicity on four cancer cells at submicromolar concentrations. The most potent derivative 3n has been shown to inhibited V-ATPase activity, migration and invasion abilities on MGC-803 cells at 0.75 mM. Conclusion: The collective results clearly indicate that heterocyclic derivatives of diphyllin inhibit the viability, V-ATPase activity, migration and invasion of the MGC803 cells. The current findings provide valuable insights for the future development of novel diphyllin derivatives as anticancer agents.

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Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers

Cancers ◽

10.3390/cancers13184563 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4563

Author(s):

Nikoletta Szemerédi ◽

Simona Dobiasová ◽

Noemi Salardón-Jiménez ◽

Annamária Kincses ◽

Márta Nové ◽

...

Keyword(s):

Wound Healing ◽

Atpase Activity ◽

Cancer Cells ◽

Anticancer Agents ◽

Biological Assessment ◽

One Pot ◽

Potential Applications ◽

Induced Apoptosis ◽

Derivatives Of ◽

Target Activity

Fifteen selenocompounds, comprising of eight ketone-containing selenoesters (K1–K8, also known as oxoselenoesters) and seven cyano-containing selenoesters (N1–N7, known also as cyanoselenoesters), have been designed, synthesized, and evaluated as novel anticancer agents. These compounds are derivatives of previously reported active selenoesters and were prepared following a three-step one-pot synthetic route. The following evaluations were performed in their biological assessment: cytotoxicity determination, selectivity towards cancer cells in respect to non-cancer cells, checkerboard combination assay, ABCB1 inhibition and inhibition of ABCB1 ATPase activity, apoptosis induction, and wound healing assay. As key results, all the compounds showed cytotoxicity against cancer cells at low micromolar concentrations, with cyanoselenoesters being strongly selective. All of the oxoselenoesters, except K4, were potent ABCB1 inhibitors, and two of them, namely K5 and K6, enhanced the activity of doxorubicin in a synergistic manner. The majority of these ketone derivatives modulated the ATPase activity, showed wound healing activity, and induced apoptosis, with K3 being the most potent, with a potency close to that of the reference compound. To summarize, these novel derivatives have promising multi-target activity, and are worthy to be studied more in-depth in future works to gain a greater understanding of their potential applications against cancer.

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Triple action Pt(iv) derivatives of cisplatin: a new class of potent anticancer agents that overcome resistance

Chemical Science ◽

10.1039/c8sc00428e ◽

2018 ◽

Vol 9 (18) ◽

pp. 4299-4307 ◽

Cited By ~ 52

Author(s):

Emanuele Petruzzella ◽

Roman Sirota ◽

Irene Solazzo ◽

Valentina Gandin ◽

Dan Gibson

Keyword(s):

Cancer Cells ◽

Anticancer Agents ◽

Single Agent ◽

Cellular Processes ◽

New Class ◽

Derivatives Of

A series of triple action Pt(iv) prodrugs was designed to test the hypothesis that multi-action compounds, where each bioactive moiety intervenes in several cellular processes, might be more effective than a single agent at killing cancer cells.

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Berberine Inhibits the Expression of SCT through miR-214-3p Stimulation in Breast Cancer Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2817147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Congyuan Zhu ◽

Jianping Li ◽

Yuming Hua ◽

Jingli Wang ◽

Ke Wang ◽

...

Keyword(s):

Breast Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Protein Levels ◽

Transwell Invasion Assay ◽

Underlying Mechanisms ◽

Mcf 7

In this study, we aimed to evaluate the suppressive abilities of berberine (BBR) on MCF-7 and MDA-MB-231 cells and confirm its underlying mechanisms on miR-214-3p. We first built a panel of 18 miRNAs and 9 lncRNAs that were reported to participate in the mechanism of breast cancer. The RT-qPCR results suggested that BBR illustrated a dosage-dependent pattern in the stimulation to miR-214-3p in both MCF-7 and MDA-MB-231 cells. Then, we performed gain-and-lose function tests to validate the role of miR-214-3p contributing to the anticancer effects of BBR. Both BBR and miR-214-3p mimic reduced the cell viability, repressed migration and invasion capacities, increased rates of total apoptotic cells and ratio of Bax/Bcl-2, and increased the percentage of G2/M cells of MCF-7 and MDA-MB-231 cells by colony formation and CKK8 assay, scratch wound healing and gelatin-based 3D conformation assay, transwell invasion assay, and cell cycle analysis, respectively. However, miR-214-3p inhibitor counteracted all these effects of BBR. Based on the bioinformatics analysis and dual-luciferase reporter test, we identified binding sites between SCT and miR-214-3p. We further confirmed that BBR massively and dose-dependently reduced the mRNA expression and protein levels of SCT in both MCF-7 and MDA-231 cells. We testified that both miR-214-3p mimic and BBR could decrease the mRNA expression and protein levels of SCT, while miR-214-3p inhibitor weakened these reductions. In conclusion, BBR suppressed MCF-7 and MDA-MB-231 breast cancer cells by upregulating miR-214-3p and increasing its inhibition to SCT.

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723: Chemokine Receptor CXCR4 Mediates Migration and Invasion of Bladder Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)37972-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 192-192 ◽

Cited By ~ 2

Author(s):

Margitta Retz ◽

Sukhvinder S. Sidhu ◽

Gregory M. Dolganov ◽

Jan Lehmann ◽

Peter R. Carroll ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Chemokine Receptor ◽

Migration And Invasion ◽

Chemokine Receptor Cxcr4 ◽

Bladder Cancer Cells

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WITHDRAWN: Silencing of Interferon-Induced Transmembrane Protein 1 (IFITM1) Inhibits Proliferation, Migration, and Invasion in Lung Cancer Cells

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x14844360974116 ◽

2017 ◽

Cited By ~ 4

Author(s):

Bing Jin ◽

Hua Jin ◽

Jing Wang

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Transmembrane Protein ◽

Lung Cancer Cells ◽

Migration And Invasion

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Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

Current Cancer Drug Targets ◽

10.2174/1568009618666180430144441 ◽

2018 ◽

Vol 19 (1) ◽

pp. 26-40 ◽

Cited By ~ 9

Author(s):

A.P. Alves ◽

A.C. Mamede ◽

M.G. Alves ◽

P.F. Oliveira ◽

S.M. Rocha ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Cells ◽

Anticancer Agents ◽

Glucose Transporter ◽

Public Health Problem ◽

High Morbidity ◽

Curative Intent ◽

Malignant Liver Tumor ◽

Glucose Transporter 1 ◽

Inhibition Of Glycolysis

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

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New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190220123547 ◽

2020 ◽

Vol 17 (2) ◽

pp. 124-137 ◽

Cited By ~ 2

Author(s):

Adel Mahmoud Attia ◽

Ahmed Ibrahin Khodair ◽

Eman Abdelnasser Gendy ◽

Mohammed Abu El-Magd ◽

Yaseen Ali Mosa Mohamed Elshaier

Keyword(s):

Dna Damage ◽

Anticancer Agents ◽

Active Compound ◽

Docking Study ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Antiviral Activities ◽

Active Methylene ◽

Damage Study

Background:Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.Objective:The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.Methods:A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.Results:The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.Conclusion:Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

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Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181112121058 ◽

2019 ◽

Vol 19 (4) ◽

pp. 439-452 ◽

Cited By ~ 3

Author(s):

Mohamed R. Selim ◽

Medhat A. Zahran ◽

Amany Belal ◽

Moustafa S. Abusaif ◽

Said A. Shedid ◽

...

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Caspase 3 ◽

Biological Evaluation ◽

Tubulin Polymerization ◽

Design Synthesis ◽

Chemical Structures ◽

M Phase ◽

Induced Apoptosis ◽

Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

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Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999201103201008 ◽

2020 ◽

Vol 20 ◽

Author(s):

Vasil Tsanov ◽

Hristo Tsanov

Keyword(s):

Cell Membrane ◽

Cancer Cells ◽

Cancer Cell ◽

Quantum Chemical ◽

Density Functional ◽

Enzyme Regulation ◽

Amide Derivatives ◽

Pass Through ◽

Hydrolysis Of ◽

Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

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