Novel Hybrid Compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide with Antimetastatic and Cytotoxic Action: Synthesis and Anticancer Screening

2019 ◽  
Vol 18 (10) ◽  
pp. 1495-1504 ◽  
Author(s):  
Yurii L. Zborovskii ◽  
Viktor V. Orysyk ◽  
Iuliia Golovynska ◽  
Olena I. Dzhus ◽  
Liudmyla V. Garmanchuk ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Antitumor Agents ◽  
Morphological Properties ◽  
Cytotoxic Action ◽  
Adhesive Properties ◽  
Hybrid Compound ◽  
Antiproliferative Agent ◽  
High Fraction

Background: One of the most promising strategies to develop multi-targeted anticancer therapeutics is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different mechanisms. Objective: To design, synthesize and perform screening of a novel hybrid anticancer compound. Method: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-μ as control anticancer agents. Results: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases. Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly inhibited the metastasizing process that was manifested by a reduction in the number and volume of metastases. Conclusions: The obtained results demonstrate that our compound can serve as a base for further structure optimization in order to design new highly-effective antimetastatic and antitumor agents.

Novel Thiazine Substituted 9-Anilinoacridines: Synthesis, Antitumour Activity and Structure Activity Relationships

2019 ◽  
Vol 19 (11) ◽  
pp. 1350-1358 ◽  
Author(s):  
R. Kalirajan ◽  
K. Gaurav ◽  
A. Pandiselvi ◽  
B. Gowramma ◽  
S. Sankar
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Antitumour Activity ◽  
Human Tumor ◽  
Cytotoxic Activities ◽  
Anti Tumour Activity ◽  
Tumour Activity

Background: 9-anilinoacridines are acting as DNA-intercalating agents which plays an important role as antitumor drugs, due to their anti-proliferative properties. Some anticancer agents contain 9- anilinoacridines such as amsacrine (m-AMSA), and nitracrine (Ledakrine) have been already developed. Methods: In this study, novel 9-anilinoacridines substituted with thiazines 4a-r were designed, synthesized, characterized by physical and spectral data and their cytotoxic activities against DLA cell lines were evaluated. Results: Among those compounds, 4b, c, e, g, i, j, k, m, o, p, q, r exhibited significant short term in vitro cytotoxic activity against Daltons lymphoma ascites (DLA) cells with CTC50 value of 0.18 to 0.31μM. The compounds 4b, c, e, g, i, j, k, m, o, p, q, r are also exhibited significant long term in vitro anti-tumour activity against human tumor cell lines, HEp-2 (laryngeal epithelial carcinoma) by Sulforhodamine B assay with CTC50 value of 0.20 to 0.39μM. The compounds 4b, i, j exhibited significant in vivo antitumor activity with % Increase in Life Span (ILS) 48-82%. Conclusion: Results obtained in this study clearly demonstrated that many of the thiazine substituted 9- anilinoacridines exert interesting anti-tumour activity. The compounds 4b, i, j have significant anti-tumour activity and useful drugs after further refinement. The above derivatives will encourage to design future antitumor agents with high therapeutic potentials.

TISSUE CULTURE AND THE STUDY OF ANTICANCER AGENTS

1966 ◽  
Vol 44 (2) ◽  
pp. 339-343 ◽  
Author(s):  
Susan Tolnai
Keyword(s):  
Fatty Acids ◽  
Tumor Cells ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Unsaturated Fatty Acids ◽  
Ascites Tumor ◽  
Mouse Tumors ◽  
Arachidonic Acids

In a quest for potential antitumor agents, more than 100 fatty acids and their derivatives were tested against transplantable mouse tumors with both in vivo and in vitro methods. Three compounds, 2,3-decenoic acid, linoleic acid, and linolenic acid, were found to arrest the growth of three types of ascites tumor cells, while 2-nonenoic, 10-undecenoic, oleic, and arachidonic acids were effective to a varying degree. The cytotoxic effects of these unsaturated fatty acids on monolayer cultures of Ehrlich ascites tumor cells and of normal mouse embryos were evaluated in experiments in which graded concentrations of the test materials incorporated in the culture medium were used.

scholarly journals Novel selective anticancer agents based on Sn and Au complexes. Mini-review

2020 ◽  
Vol 92 (8) ◽  
pp. 1201-1216
Author(s):  
Elena R. Milaeva ◽  
Dmitry B. Shpakovsky ◽  
Yulia A. Gracheva ◽  
Taisiya A. Antonenko ◽  
Tatyana D. Ksenofontova ◽  
...  
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Inorganic Compounds ◽  
Acquired Resistance ◽  
Cytotoxic Action ◽  
Mitochondrial Potential ◽  
Anti Cancer ◽  
Gold Compounds

AbstractCancer is one of the most common causes of death in modern medicine. Molecular design of novel substances with pharmacological activity is one of the goals of medicinal inorganic chemistry. Platinum complexes are widely used in the treatment of cancer, despite high efficacy their use is limited by side effects, as well as primary or acquired resistance. In this regard, the search for novel metal-containing antitumor compounds is underway. Organotins and gold compounds are promising pharmacological agents with anti-cancer properties. The introduction of protective antioxidant fragments into inorganic compounds molecules is a way to reduce the side effects of anti-cancer drugs on healthy cells. 2,6-dialkylphenols belonging to vitamin E (α-tocopherol) mimetics are widely used as antioxidants and stabilizers. The properties of Ph3SnCl (Sn-I), Ph3PAuCl (Au-I) and complexes Ph3SnSR (Sn-II) and Ph3PAuSR (Au-II) based on 2,6-di-tert-butyl-4-mercaptophenol (RSH) as radical scavengers and reducing agents were studied in model reactions. For Sn-II and Au-II the comparative study of cytotoxic action was made and the IC50 values on different cancer cell lines were found to be depended on the nature of metal. In general, Sn(IV) complexes possessed higher cytotoxicity than Au(I) complexes. In order to clarify the mechanism of cytotoxic mode of action the effect of compounds on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability, cell cycle and induction of apoptosis was studied. Organotin compounds can bind tubulin SH-groups and inhibit its polymerization by a dose-dependent mechanism, whereas gold compounds inhibit Thioredoxin reductase (TrxR). In vivo experiments on acute toxicity of Sn-II and Au-II proved their moderate toxic action that opens prospects for the further study as antitumor agents.

Stilbenes and Xanthones from Medicinal Plants as Potential Antitumor Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Eugenia Dumitra Teodor ◽  
Oana Ungureanu ◽  
Veronica Moroeanu ◽  
Gabriel Lucian Radu
Keyword(s):  
Medicinal Plants ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Plant Polyphenols ◽  
Natural Substances ◽  
Abnormal Cells ◽  
Digestive Disorders ◽  
Potential Antitumor

Abstract:: There is an emerging interest for plant polyphenols as dietary ingredients, particularly in digestive disorders and/or as antitumor agents. The plant compounds or extracts continue to be an alternative to drug use, many studies being aimed to find natural substances with selective cytotoxicity on abnormal cells. Phenolic compounds as important secondary metabolites from plants are intensively studied as substitute of drugs. In this review, the recent literature data from past five years about potential anticancer/antitumor effect of some categories of phenolics such as stilbenes and xanthones extracted from medicinal plants are surveyed. The most important results concerning the effectiveness as antitumor/anticancer agents of these active compounds, as isolated compounds or as plant extracts, some bioavailability aspects and their mechanism of action in vitro and in vivo were considered.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

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.

Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cdk Inhibitors ◽  
Comprehensive Overview ◽  
P53 Expression ◽  
Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

scholarly journals Activity of Indenoisoquinolines against African Trypanosomes

2008 ◽  
Vol 53 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Rahul P. Bakshi ◽  
Dongpei Sang ◽  
Andrew Morrell ◽  
Mark Cushman ◽  
Theresa A. Shapiro
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Sleeping Sickness ◽  
Water Soluble ◽  
African Trypanosomes ◽  
In Vivo Experiments ◽  
Topoisomerase Ib ◽  
Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

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