An Overview of Privileged Scaffold: Quinolines and Isoquinolines in Medicinal Chemistry as Anticancer Agents

2020 ◽  
Vol 20 (28) ◽  
pp. 2599-2633
Author(s):  
Yanna Mao ◽  
Kunjal Soni ◽  
Chetan Sangani ◽  
Yongfang Yao
Keyword(s):  
Cancer Treatment ◽  
Anticancer Agents ◽  
Causes Of Death ◽  
Antitumor Agents ◽  
Antitumor Agent ◽  
New Drugs ◽  
Current Scenario ◽  
Anticancer Treatment ◽  
Privileged Scaffold ◽  
Isoquinoline Derivatives

: Cancer is one of the most difficult diseases and causes of death for many decades. Many pieces of research are continuously going on to get a solution for cancer. Quinoline and isoquinoline derivatives have shown their possibilities to work as an antitumor agent in anticancer treatment. The members of this privileged scaffold quinoline and isoquinoline have shown their controlling impacts on cancer treatment through various modes. In particular, this review suggests the current scenario of quinoline and isoquinoline derivatives as antitumor agents and refine the path of these derivatives to find and develop new drugs against an evil known as cancer.

scholarly journals Translational Research in Cancer Drug Development

2011 ◽  
Vol 2 (2) ◽  
pp. 198
Author(s):  
Edy Meiyanto ◽  
Adam Hermawan ◽  
Anindyajati Anindyajati
Keyword(s):  
Targeted Therapy ◽  
Drug Development ◽  
Cancer Treatment ◽  
Rapid Development ◽  
Antitumor Agent ◽  
New Drugs ◽  
Cancer Drug ◽  
Cell Growth And Differentiation ◽  
High Level ◽  
Drug Development Research

The development of cancer treatment were initiated by the existence of human’s effort to treat by applying certain materials which is mostly part(s) or extracts of plants, which are now adapted as traditional herbal medicine. The discovery of new drugs was based on intuition and empirical evidence. Thus, high luck factor was involved in a successful treatment with unguaranteed reproducibility. One example of drug being developed through conventional drug development is Taxol. Taxol is an extremely complex natural product and requires a bunch of hard work with high level of serendipity to be discovered as antitumor agent. Recently, rapid development in human biology and technology allow a change in drug discovery strategy by minimizing the luck factor. Targeted therapy has been a very promising strategy of drug development research, especially in cancer treatment. Although cancer has been known as a disease with very complex cellular and histo-pathophysiology, the abundance of studies on proteins, such as receptors and hormones, as the hallmarks of cancer allows us to explore carcinogenesis suppression further based on molecular targeted therapy. Kinases, one type of protein involved in signal transduction regulating cell growth and differentiation, could be the proteins that are proposed to be inhibited in suppressing tumor growth. An interesting example of the drug being discovered based on molecular modeling is the discovery of lapatinib as anti- cancer with specific target on HER-2 and EGFR to overcome the resistance of cancer to Herceptin caused by elevated level of EGFR expression.Keywords : targeted therapy, cancer, translational drug development

scholarly journals The Role of Low Energy Electrons in Radiobiology and Cancer Treatment

2021 ◽  
Author(s):  
Sasan Esmaili ◽  
Farzaneh Allaveisi
Keyword(s):  
Cancer Treatment ◽  
Anticancer Agents ◽  
High Energy ◽  
Low Energy ◽  
New Drugs ◽  
Particle Radiation ◽  
Energy Radiation ◽  
Regulatory Pathways ◽  
High Energy Electrons ◽  
Low Energy Electrons

Low energy radiation can be produced by all types of high energy radiation. Studies of low energy particle radiation help us to understand the chemistry induced by high energy radiations. Low energy electrons are capable of chemical selectivity in contrast to high energy electrons due to the large number of open dissociative channels in the former case and their resonant nature. Among different types of radiation, low energy electrons have a higher cross-section to DNA damage and they have an important role in the synergistic effect between radiation and chemotherapy anticancer agents in cancer treatment. Analysis of these combined records helps assign function of cells, identify metabolic and regulatory pathways and suggest targets for diagnostics and therapeutics identify animal models to develop new drugs, among other goals of biomedical interest.

Known Triterpenes and their Derivatives as Scaffolds for the Development of New Therapeutic Agents for Cancer

2018 ◽  
Vol 25 (10) ◽  
pp. 1259-1269 ◽  
Author(s):  
Gregorio Peron ◽  
Giovanni Marzaro ◽  
Stefano Dall`Acqua
Keyword(s):  
Secondary Metabolites ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Tumor Development ◽  
Therapeutic Agents ◽  
Cellular Growth ◽  
New Drugs ◽  
Inflammatory Processes ◽  
And Migration

Background: Plants produce several bioactive secondary metabolites whose are used as therapeutic agents to treat several diseases, among whom cancer. Triterpenes are secondary metabolites that exert inhibitory activity against multiple intracellular and extracellular targets in euchariotic cells. These targets are proteins involved in apoptosis, cell development and differentiation, angiogenesis, metastasis and inflammatory processes. The inhibition of their functions leads to decreased cellular growth, differentiation and migration, resulting in antitumor activity, as shown by several authors. Furthermore, during recent years synthetic triterpenoid derivatives have also been developed to implement potency and efficacy of starting compounds, allowing the obtainment of new agents having promising anticancer activity. Objective: In this review we report the latest results regarding anticancer activity of some of the most studied triterpenes in the field, as well as of their semi-synthetic derivatives, with the aim to summarize the role of triterpenes as molecular leads for the development of new classes of antitumor agents. Methods: We focused on the most recent literature regarding triterpenes in cancer treatment, highlighting the potential of developing new drugs starting from these natural compounds. Conclusion: Several “old” triterpenes as ursolic, betulinic and oleanolic acids were recently reconsidered as model compounds for the development of innovative anticancer agents. Their activity against proteins involved in tumor development enhances the opportunity to exploit these compounds as new multi-target therapeutic agents. Furthermore, the possibility to synthetize new compounds from their natural-occurring structures could be an alternative to overcome cellular resistance to drugs and could improve their therapeutic efficacy.

Selective Cytotoxic Effects of 5-Trifluoromethoxy-1H-indole-2,3-dione 3-Thiosemicarbazone Derivatives on Lymphoid-originated Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Ferdane Danışman-Kalındemirtaş ◽  
Serap Erdem-Kuruca ◽  
Kadriye Akgün-Dar ◽  
Zeynep Karakaş ◽  
Özge Soylu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cell Lines ◽  
Anticancer Agents ◽  
K562 Cell ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Myelogenous Leukemia ◽  
Lymphoma Cells ◽  
Cytotoxic Effects ◽  
Compound C

Aim: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3-thiosemicarbazone derivatives. These compounds could be promissing anticancer agents in leukemia treatment. Background : Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to non-specificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life. Method: In this study, the anticancer effects of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives (A-L) were investigated in chronic myelogenous leukemia K562, Burkitt’s lymphoma P3HR1, acute promyelocytic leukemia HL60 cells and vincristine-resistant sublines of K562 and P3HR1 cells. Additionally, the compounds were tested on lymphoid derived cells from ALL patients. In order to investigate the particular mechanism of death caused by the cytotoxic effects of the compounds, immunohistochemical caspase 3 staining was performed in P3HR1 cells, and resulting apoptotic activities were demonstrated. Result: All compounds tested have been found to have cytotoxic effects against lymphoma cells at submicromolar concentrations (IC50= 0.89-1.80 µM). Most compounds show significant selectivity for the P3HR1 and P3HR1 Vin resistant. The most effective and selective compound is 4-bromophenyl substituted compound I (IC50=0.96 and 0.89 µM). Cyclohexyl and benzyl substituted compounds D and E have also been found to have cytotoxic effects against K562 cell lines (IC50=2.38 µM), while the allyl substituted compound C is effective on all cell lines (IC50=1.13-2.21 µM). 4-Fluorophenyl substituted F compound has been observed to be effective on all cells (IC50=1.00-2.41 µM) except K562 cell. Compound C is the only compound that shows inhibition of HL-60 cells (IC50= 1.13 µM). Additionally, all compounds exhibited cytotoxic effects on lymphoid-derived cells at 1µM concentration. These results are in accordance with the results obtained in lymphoma cells. Conclusion: All compounds tested have submicromolar concentrations of cytotoxic effects on cells. These compounds hold promise for the future treatment of leukemia cancer.

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma

2019 ◽  
Vol 20 (3) ◽  
pp. 197-214 ◽  
Author(s):  
Isabel Sánchez-Crisóstomo ◽  
Eduardo Fernández-Martínez ◽  
Raquel Cariño-Cortés ◽  
Gabriel Betanzos-Cabrera ◽  
Rosa A. Bobadilla-Lugo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Anticancer Agents ◽  
Liver Diseases ◽  
Membrane Receptors ◽  
New Drugs ◽  
Sexual Hormones ◽  
Steroid Nucleus ◽  
Alcoholic Fatty Liver ◽  
Prevention And Treatment

Background: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1380-1392
Author(s):  
Emine Merve Güngör ◽  
Mehlika Dilek Altıntop ◽  
Belgin Sever ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Antitumor Agents ◽  
Colorimetric Assay ◽  
Fibroblast Cell ◽  
Lipinski’S Rule ◽  
In Silico Docking ◽  
Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

Synthesis and Biological Evaluation of Novel 4,5,6,7-Tetrahydrobenzo[D]-Thiazol-2- Yl Derivatives Derived from Dimedone with Anti-Tumor, C-Met, Tyrosine Kinase and Pim-1 Inhibitions

2019 ◽  
Vol 19 (12) ◽  
pp. 1438-1453 ◽  
Author(s):  
Rafat M. Mohareb ◽  
Amr S. Abouzied ◽  
Nermeen S. Abbas
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Cell Lines ◽  
Single Molecule ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
New Drugs ◽  
Tumor Cell Lines ◽  
Thiazole Derivatives ◽  
Wide Range

Background: Dimedone and thiazole moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. Thiazole derivatives are a very important class of compounds due to their wide range of pharmaceutical and therapeutic activities. On the other hand, dimedone is used to synthesize many therapeutically active compounds. Therefore, the combination of both moieties through a single molecule to produce heterocyclic compounds will produce excellent anticancer agents. Objective: The present work reports the synthesis of 47 new substances belonging to two classes of compounds: Dimedone and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. To achieve this goal, our strategy was to synthesize a series of 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivatives using the reaction of the 2-bromodimedone with cyanothioacetamide. Methods: The reaction of 2-bromodimedone with cyanothioacetamide gave the 4,5,6,7-tetrahydrobenzo[d]- thiazol-2-yl derivative 4. The reactivity of compound 4 towards some chemical reagents was observed to produce different heterocyclic derivatives. Results: A cytotoxic screening was performed to evaluate the performance of the new derivatives in six tumor cell lines. Thirteen compounds were shown to be promising toward the tumor cell lines which were further evaluated toward five tyrosine kinases. Conclusion: The results of antitumor screening showed that many of the tested compounds were of high inhibition towards the tested cell lines. Compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 21b, 21c, 20d and 21d were the most potent compounds toward c-Met kinase and PC-3 cell line. The most promising compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 20c, 20d, 21b, 21c and 21d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6c, 11b, 11d, 14b, 15c, and 20d were selected to examine their Pim-1 kinase inhibition activity the results revealed that compounds 11b, 11d and 15c had high activities.

Does the Oxazolidinone Derivatives Constitute a Functional Approach for Cancer Therapy?

2020 ◽  
Vol 7 (2) ◽  
pp. 95-106
Author(s):  
Eduardo Augusto Vasconcelos de Freitas Ramalho ◽  
Marina Galdino da Rocha Pitta ◽  
Hernando de Barros Siqueira Neto ◽  
Ivan da Rocha Pitta
Keyword(s):  
Cell Lines ◽  
Antitumor Agents ◽  
Partial Agonist ◽  
Drug Repurposing ◽  
Antitumor Agent ◽  
Short Review ◽  
Sphingolipid Metabolism ◽  
Solid Cancer ◽  
Ppar Γ ◽  
Anti Cancer

In the last four decades, the emphasis was laid on the research of small organic molecules with potential anti-cancer activity. Linezolid was the first oxazolidinone derivative approved by FDA for MRSA treatment. Despite its major role in antimicrobial activity, these molecules display other properties, also serving as an antitumor agent. The importance of drug repurposing could be highlighted by the use of Oxazolidinone derivatives in pre-clinical studies, which are able to act through different pathways, such as partial agonist of transcription factor PPAR-γ, an inhibitor of key enzymes related to hormone-dependent disorders and even on sphingolipid metabolism as well. The purpose of this short review is to discuss the application of oxazolidinone derivatives as an antitumor agent by highlighting the most promising molecules studied by many research groups worldwide. Main biological activity against several tumor cell lines, including hematopoietic and solid cancer cell lines have been discussed. In addition, this study intends to report how different types of oxazolidinone derivatives can act as antitumor agents describing their distinct mechanisms of action based on their targets.

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