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

Cancers ◽  
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.

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

2020 ◽  
Vol 17 ◽  
Author(s):  
Weidong Shen ◽  
Haijiao Chen ◽  
Miaomiao Wu ◽  
Ting Zhang ◽  
Li Zhu ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Migration And Invasion ◽  
Transwell Invasion Assay ◽  
Atpase Inhibitors ◽  
Scratch Wound ◽  
Heterocyclic Derivatives ◽  
Antiviral Activities ◽  
Derivatives Of

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.

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

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
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.

Ester derivatives of salinomycin efficiently eliminate breast cancer cells via ER-stress-induced apoptosis

2021 ◽  
Vol 893 ◽  
pp. 173824
Author(s):  
Dominika Kuran ◽  
Sylwia Flis ◽  
Michał Antoszczak ◽  
Marlena Piskorek ◽  
Adam Huczyński
Keyword(s):  
Breast Cancer ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Induced Apoptosis ◽  
Derivatives Of

scholarly journals A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5581
Author(s):  
Raju Suresh Kumar ◽  
Dhaifallah M. Al-thamili ◽  
Abdulrahman I. Almansour ◽  
Natarajan Arumugam ◽  
Faruq Mohammad
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
One Pot ◽  
Major Pathway ◽  
Molecular Scaffold ◽  
Highly Active ◽  
Ft Ir ◽  
Derivatives Of ◽  
Unique Mechanism

With an aim to develop more effective and affordable anticancer agents possessing a unique mechanism of action, we designed and synthesized derivatives of spirooxindole-pyrrolidine heterocyclic hybrids in good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 µg/mL concentration. The highly active molecular scaffold was tested for the in-depth mechanistic studies, and it was found that the major pathway of cell death is apoptosis which occurs through the induction of reactive oxygen species followed by the involvement of caspases.

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

2018 ◽  
Vol 9 (18) ◽  
pp. 4299-4307 ◽  
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.

scholarly journals Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4138
Author(s):  
Sheng-You Li ◽  
Ze-Kun Sun ◽  
Xue-Yi Zeng ◽  
Yue Zhang ◽  
Meng-Ling Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Furan Ring ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Prostate Cancer Cells ◽  
One Pot ◽  
Synthetic Strategy ◽  
Induced Apoptosis

Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

scholarly journals One-pot, multi-component synthesis of novel 2-amino-[1,2,4]triazolo[1,5-a] pyrimidine-6-carboxamide derivatives as antiproliferative agents 

2021 ◽  
Author(s):  
Xian-Sen Huo ◽  
Yu-Feng Ma ◽  
Zhi-Ru Chen ◽  
Li-Li Yuan ◽  
Xiao-Lan Zheng ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Inhibition Activity ◽  
Cell Growth Inhibition ◽  
Cancer Cell Growth ◽  
One Pot ◽  
Antiproliferative Agents ◽  
Heterocyclization Reaction ◽  
Growth Inhibition Activity

Abstract A novel series of 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide derivatives has been achieved successfully via an efficient one-pot three-component Biginelli-like heterocyclization reaction between different benzaldehydes, 1H-1,2,4-triazole-3,5-diamine, and N-substituted acetoacetamides in the presence of p-toluenesulfonic acid as a catalyst. Moreover, the effects of different conditions on the reaction were well investigated. In addition, cancer cell growth inhibition activity for these target compounds was also explored, and analogue 5l demonstrated the most potent cytotoxic activity against different cancer cells. These finds indicat that 2-amino-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxamide core could be well worth further optimization as a potential scaffold for development of anticancer agents.

scholarly journals Evidence in Support of Potential Applications of Lipid Peroxidation Products in Cancer Treatment

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Omotayo O. Erejuwa ◽  
Siti A. Sulaiman ◽  
Mohd S. Ab Wahab
Keyword(s):  
Lipid Peroxidation ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Anticancer Agents ◽  
Cancer Recurrence ◽  
Current Treatment ◽  
Lipid Peroxidation Products ◽  
Treatment Regimens ◽  
Potential Applications

Cancer cells generate reactive oxygen species (ROS) resulting from mitochondrial dysfunction, stimulation of oncogenes, abnormal metabolism, and aggravated inflammatory activities. Available evidence also suggests that cancer cells depend on intrinsic ROS level for proliferation and survival. Both physiological and pathophysiological roles have been ascribed to ROS which cause lipid peroxidation. In spite of their injurious effects, the ROS and the resulting lipid peroxidation products could be beneficial in cancer treatment. This review presents research findings suggesting that ROS and the resulting lipid peroxidation products could be utilized to inhibit cancer growth or induce cancer cell death. It also underscores the potential of lipid peroxidation products to potentiate the antitumor effect of other anticancer agents. The review also highlights evidence demonstrating other potential applications of lipid peroxidation products in cancer treatment. These include the prospect of lipid peroxidation products as a diagnostic tool to predict the chances of cancer recurrence, to monitor treatment progress or how well cancer patients respond to therapy. Further and detailed research is required on how best to successfully, effectively, and selectively target cancer cells in humans using lipid peroxidation products. This may prove to be an important strategy to complement current treatment regimens for cancer patients.

scholarly journals Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 92
Author(s):  
Ismael Obaidi ◽  
Hilary Cassidy ◽  
Verónica Ibáñez Gaspar ◽  
Jasmin McCaul ◽  
Michael Higgins ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Kidney Cancer ◽  
Anticancer Agents ◽  
Combination Treatment ◽  
Zebrafish Embryo ◽  
Death Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Embryo Viability ◽  
Induced Apoptosis

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a selective anticancer cytokine capable of exerting a targeted therapy approach. Disappointingly, recent research has highlighted the development of TRAIL resistance in cancer cells, thus minimising its usefulness in clinical settings. However, several recent studies have demonstrated that cancer cells can be sensitised to TRAIL through the employment of a combinatorial approach, utilizing TRAIL in conjunction with other natural or synthetic anticancer agents. In the present study, the chemo-sensitising effect of curcumin on TRAIL-induced apoptosis in renal carcinoma cells (RCC) was investigated. The results indicate that exposure of kidney cancer ACHN cells to curcumin sensitised the cells to TRAIL, with the combination treatment of TRAIL and curcumin synergistically targeting the cancer cells without affecting the normal renal proximal tubular epithelial cells (RPTEC/TERT1) cells. Furthermore, this combination treatment was shown to induce caspase-dependent apoptosis, inhibition of the proteasome, induction of ROS, upregulation of death receptor 4 (DR4), alterations in mitogen-activated protein kinase (MAPK) signalling and induction of endoplasmic reticulum stress. An in vivo zebrafish embryo study demonstrated the effectiveness of the combinatorial regime to inhibit tumour formation without affecting zebrafish embryo viability or development. Overall, the results arising from this study demonstrate that curcumin has the ability to sensitise TRAIL-resistant ACHN cells to TRAIL-induced apoptosis.

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