Synthesis of substituted phenanthrene-9-benzimidazole conjugates: Cytotoxicity evaluation and apoptosis inducing studies

Kumar, Nitin; Sharma, Pankaj; Kumari, Shikha; Brahma, Umarani; Nekkanti, Shalini; Shankaraiah, Nagula; Kamal, Ähmed

doi:10.1016/j.ejmech.2017.09.006

Cited by 27 publications

(10 citation statements)

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“…and Wang et al. in their cell cycle disturbance studies 37 , 38 . An increase in the cell cycle of the G2/M phase may indicate that DNA strands have been damaged, which is compatible with one of the mechanisms of cisplatin 23 .…”

Section: Discussionmentioning

confidence: 97%

A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

Czarnomysy

Surażyński

Muszyńska

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Six novel compounds of platinum(II) with pyrazole derivatives PtPz1–PtPz6 were synthesised and characterised (PtPz1 - [Pt2N-hydroksymethyl-3,5-dimethylpyrazole4(berenil)2]Cl4; PtPz2 - [Pt23,5-dimethylpyrazole4(berenil)2]Cl4; PtPz3 - [Pt23,4-dimethylpyrazole4(berenil)2]Cl4; PtPz4 - [Pt2pyrazole4(berenil)2]Cl4; PtPz5- [Pt25-methylpyrazole4(berenil)2]Cl4; PtPz6 - [Pt2N-ethylpyrazole4(berenil)2]Cl4). The cytotoxic activity of these complexes against MCF-7 and MDA-MB-231 breast cancer cell lines was determined using the MTT assay. Evaluation of apoptosis induction was done with the Annexin V-fluorescein isothiocyanate/propidium iodide assay. In addition, using a flow cytometer, we determined the influence of test compounds on the cell cycle and caspase-3, -8, and -9 activity. The obtained results of caspase activity were confirmed by cell imaging. Moreover, using the flow cytometer, the effects of the test compounds on mitochondrial potential change were assessed. The test results showed that novel pyrazole-platinum(II) complexes exhibited stronger anti-proliferative activity against two breast cancer cell lines than reference cisplatin. Compounds PtPz1, PtPz2, and PtPz3 with methyl substituents at the pyrazole ring showed stronger activity than pyrazole or ethylpyrazole containing complexes. Studies have shown that inhibition of cell survival occurs by arresting the G1 cell cycle and inducing apoptosis. Our analysis associated with the response of MCF-7 and MDA-MB-231 cells to treatment with PtPz1–PtPz6 showed that it leads the cells through the external and intrinsic (mitochondrial) apoptotic pathway via indirect DNA damage.

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Section: Discussionmentioning

confidence: 97%

A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

Czarnomysy

Surażyński

Muszyńska

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…41 The nature of cell death induced by the formulated CuCs nanocomposite was analyzed with flow cytometry, and results showed that Huh7 treated with an IC50 concentration of nanocomposite induced cell cycle arrest at the preG1 phase in comparison to the untreated cells, which hindered their entrance into the S and G2/M phases. This might be due to the small amount of DNA content and admission into programmed cell death, as previously illustrated by Kumar et al 42 The results of molecular apoptotic gene expression level of cells treated with an IC50 concentration of curcumin and its composite showed high expression levels in caspase 3 and lowered expression of Bcl2 in Huh7 cells treated with curcumin and its nanocomposite. This indicates that the apoptosis was induced via a caspasedependent pathway.…”

Section: Discussionmentioning

confidence: 61%

<p>Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines</p>

Loutfy¹,

Elberry²,

Farroh³

et al. 2020

IJN

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Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/ mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspasedependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent. Plain Language SummaryHepatitis C virus genotype 4a (HCV-4a) is a major public health problem, especially among the Egyptian population. There are more than 70 million individuals infected worldwide. It is the leading cause of chronic liver diseases, cirrhosis, and hepatocellular carcinoma. Newly emerged anti-HCV viral agents have recently become available on the market but with serious complications, high cost, and possible development of resistance. This has encouraged scientists to search for alternative, safer antiviral approaches. Nanoparticles offer unique physical properties that have associated benefits for antimicrobial activity or as drug carrier that can improve antiviral therapy. The significance of our research is in establishment of a natural nanoparticle drug carrier system that we screened with computer simulation studies and in cells against HCV-4a replication into human hepatoblastoma cell

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“…N. P. Kumar et al [91] condensed phenanthrene aldehydes with substituted o ‐phenylene diamine to synthesize an array of novel phenanthrene‐9‐benzimidazole conjugates and screened them in vitro for their anti‐cancer potency against BT‐549 (breast cancer cell lines), PC‐3 and DU145 (prostate cancer cell lines), MDA‐MB‐453 (breast cancer cell lines), and HCT‐116 and HCT‐15 (colon cancer cell lines). Among the screened compounds, compound 68 exhibited significant cytotoxic action against PC‐3 cancer cell lines (IC 50 = 6.32 ± 0.09 μM).…”

Section: Benzimidazole As Target Oriented Anticancer Agentsmentioning

confidence: 99%

Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

Satija

Sharma

Madan

et al. 2021

Journal of Heterocyclic Chem

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Benzimidazole, the benzo derivative of imidazole, is a class of bicyclic aromatic organic compound consisting of six‐membered benzene ring fused to five‐membered imidazole at 4‐ and 5‐positions of the imidazole ring. It is a vital pharmacophore of many biologically active heterocyclic compounds with a variety of pharmacological activities. Over the time, benzimidazole and its derivatives have evolved as vibrant heterocyclic systems due to their potency in a wide range of bioactive compounds like analgesics, antifungals, anti‐inflammatory, antihypertensives, proton pump inhibitors, anti‐HIV, antiviral, and so on. Multi‐drug resistance in cancer that led to the failure of many chemotherapeutic drugs is a major concern. Various approaches are being developed to overcome this problem. One of them is target based drug discovery, which is an effective method to develop a novel anticancer drug. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last 5 years literature on benzimidazole used as anticancer agents has been reviewed and summarized in the paper herein. This review article along with the target of cancer also deal with structure activity relationship of various compounds having benzimidazole ring.

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Synthesis of substituted phenanthrene-9-benzimidazole conjugates: Cytotoxicity evaluation and apoptosis inducing studies

Cited by 27 publications

References 61 publications

A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

<p>Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines</p>

Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

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