New Heterocyclic Combretastatin A-4 Analogs: Synthesis and Biological Activity of Styryl-2(3H)-Benzothiazolones

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzothiazolone (26Z) exhibits the most potent cytotoxic activity (IC50 0.13 ± 0.01 µM) against EA.hy926 cells. 26Z not only inhibits vasculogenesis but also disrupts pre-existing vasculature. 26Z is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. 26Z also shows anti-proliferative activity in CA-4 resistant cells with the following IC50 values: HT-29 (0.008 ± 0.001 µM), MDA-MB-231 (1.35 ± 0.42 µM), and MCF-7 (2.42 ± 0.48 µM). Cell-cycle phase-specific experiments show that 26Z treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some 26Z-treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by 26Z has an exciting chemotherapeutic potential that merits further investigation.

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Cytotoxic Sterols from Philippine Mushrooms

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22591 ◽

2020 ◽

Vol 32 (5) ◽

pp. 1197-1202

Author(s):

Consolacion Y. Ragasa ◽

Glenn G. Oyong ◽

Maria Carmen S. Tan ◽

Mariquit M. De Los Reyes ◽

Maria Ellenita G. De Castro

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Dermal Fibroblast ◽

Cancer Cell Lines ◽

Cytotoxic Activities ◽

Cell Viability Assay ◽

Ic50 Values ◽

Ht 29 ◽

Mcf 7

Ergosterol peroxide (1) and ergosterol (2) were commonly isolated as the major compounds of Philippine mushrooms. Sterols 1 and 2 from the dichloromethane extract of Geastrum triplex and Termitomyces clypeatus, respectively, were evaluated for their cytotoxic activities against four human cancer cell lines, viz., breast cancer (MCF-7), colon cancer (HT-29), leukemia (THP-1), and small lung cell carcinoma (H69PR), and a human normal cell line, human dermal fibroblast-neonatal (HDFn), using the PrestoBlue® cell viability assay. Compounds 1 and 2 exhibited the strongest activities against HT-29 with IC50 values of 1.79 and 2.98 μg/mL, respectively, while Zeocin gave an IC50 of 4.89 μg/mL. These compounds also exhibited strong antiproliferative effects against MCF-7 with IC50 values of 4.13 for 1 and 4.20 μg/mL for compound 2, comparable to Zeocin with IC50 = 3.68 μg/mL. Only moderate cytotoxicity resulted when compounds 1 and 2 were tested against H69PR with IC50 values of 7.78 and 6.83 μg/mL, respectively, while Zeocin exhibited an IC50 of 9.81 μg/mL. Furthermore, compounds 1 and 2 showed no effects against THP-1 (IC50 > 100 μg/mL), while Zeocin showed an IC50 of 4.73 μg/mL. Although compounds 1 and 2 have been reported to exhibit different bioactivities in previous studies, the cancer cell lines tested and/or the polarities of the solvents for extraction varied. Therefore, comparisons of the cytotoxic activities of compounds 1 and 2 with earlier studies could not be made extensively.

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Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

Bulletin of the Chemical Society of Ethiopia ◽

10.4314/bcse.v34i2.14 ◽

2020 ◽

Vol 34 (2) ◽

pp. 377-384

Author(s):

B. Taheri ◽

M. Taghavi ◽

M. Zarei ◽

N. Chamkouri ◽

A. Mojaddami

Keyword(s):

Molecular Docking ◽

Cytotoxic Activity ◽

Cell Lines ◽

Biological Activities ◽

Docking Studies ◽

Carbazole Derivatives ◽

Ic50 Values ◽

Docking Energy ◽

Ht 29 ◽

Mcf 7

Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.8396 and R2 = 0.834, respectively. Docking studies of these compounds were also performed on the DNA as proposed target to comprehend their binding interactions and binding energies. The docking energy of compounds ranged from - 11.32 to -13.48 kcal/mol. Compound C3 with energy of -13.48 kcal/mol had the highest docking energy. Docking results indicated that these compounds (C1-C5) had strong affinity in binding to the DNA. KEY WORDS: Imidazole, Carbazole, Molecular docking, Cancer, MTT assay Bull. Chem. Soc. Ethiop. 2020, 34(2), 377-384 DOI: https://dx.doi.org/10.4314/bcse.v34i2.14

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Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

Medicinal Chemistry ◽

10.2174/1573406416666200817164308 ◽

2020 ◽

Vol 16 ◽

Author(s):

Délis Galvão Guimarães ◽

Arlan de Assis Gonsalves ◽

Larissa Araújo Rolim ◽

Edigênia Cavalcante Araújo ◽

Victória Laysna dos Anjos Santos ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Biological Activities ◽

Supporting Electrolyte ◽

Cancer Cell Lines ◽

Molecular Structures ◽

Cytotoxic Activities ◽

Electrochemical Studies ◽

Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

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Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells

Molecules ◽

10.3390/molecules27020369 ◽

2022 ◽

Vol 27 (2) ◽

pp. 369

Author(s):

Joanna Wawszczyk ◽

Katarzyna Jesse ◽

Sławomir Smolik ◽

Małgorzata Kapral

Keyword(s):

Colon Cancer ◽

Cell Death ◽

Cell Growth ◽

Cancer Cells ◽

Biological Activities ◽

Therapeutic Option ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Inhibition Of Proliferation ◽

Ht 29

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.

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VANILLIN EXTRACTED FROM PROSO MILLET AND BARNYARD MILLET INDUCE APOPTOSIS IN HT-29 AND MCF-7 CELL LINE THROUGH MITOCHONDRIA MEDIATED PATHWAY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i12.21088 ◽

2017 ◽

Vol 10 (12) ◽

pp. 226 ◽

Cited By ~ 3

Author(s):

Deepa Priya Ramadoss ◽

Nageswaran Sivalingam

Keyword(s):

Cell Death ◽

Cytochrome C ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Caspase 9 ◽

Cytochrome C Release ◽

Barnyard Millet ◽

Proso Millet ◽

Ht 29 ◽

Mcf 7

Objective: The main aim of the study was to investigate the bioactive compound vanillin extracted from proso millet (compound 1), and barnyard millet (compound 2) induces apoptotic cell death and whether it is mediated through mitochondrial pathway in HT-29 and MCF-7 cell line.Methods: The cells were treated with 250 μg/ml and 1000 μg/ml concentration of extracted vanillin for 48 hrs. Cytochrome c release and expression level of pro-apoptotic protein Bax and caspase-9 were detected by western blot analysis.Results: The results reveal that extracted compounds increased the release of cytochrome c and upregulating the expression of Bax and caspase-9 as concentration increases in a dose-dependent manner.Conclusion: The study suggests that the vanillin compound extracted from these millets induces apoptotic cell death through a mitochondria-dependent pathway.

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Dimeric 1,4-benzoquinone Derivatives with Cytotoxic Activities from the Marine-Derived Fungus Penicillium sp. L129

Marine Drugs ◽

10.3390/md17070383 ◽

2019 ◽

Vol 17 (7) ◽

pp. 383 ◽

Cited By ~ 1

Author(s):

Zhang ◽

Ju ◽

Li ◽

Sun ◽

Peng ◽

...

Keyword(s):

Quorum Sensing ◽

Cell Lines ◽

Inhibitory Activity ◽

Spectroscopic Data ◽

Cytotoxic Activities ◽

Penicillium Sp ◽

Ic50 Values ◽

Cytotoxicity Activities ◽

Mic Value ◽

Mcf 7

Two new dimeric 1,4-benzoquinone derivatives, peniquinone A (1) and peniquinone B (2), a new dibenzofuran penizofuran A (3), and a new pyrazinoquinazoline derivative quinadoline D (4), together with 13 known compounds (5–17), were isolated from a marine-derived fungus Penicillium sp. L129. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and electronic circular dichroism calculations. Compound 1 exhibited cytotoxicity against the MCF-7, U87 and PC3 cell lines with IC50 values of 12.39 µM, 9.01 µM and 14.59 µM, respectively, while compound 2 displayed relatively weak cytotoxicity activities against MCF-7, U87 and PC3 cell lines with IC50 values of 25.32 µM, 13.45 µM and 19.93 µM, respectively. Furthermore, compound 2 showed weak quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with an MIC value of 20 μg/well.

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Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities

Molecules ◽

10.3390/molecules24203811 ◽

2019 ◽

Vol 24 (20) ◽

pp. 3811

Author(s):

Javier E. Barúa ◽

Mercedes de la Cruz ◽

Nuria de Pedro ◽

Bastien Cautain ◽

Rosa Hermosa ◽

...

Keyword(s):

Human Hepatocytes ◽

Bioactive Molecules ◽

Cytotoxic Activities ◽

Terpene Cyclase ◽

Trichodiene Synthase ◽

Specific Step ◽

Ic50 Values ◽

Selective Antimicrobial Activity ◽

Tumorigenic Cell Line ◽

Mcf 7

Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In Trichoderma brevicompactum, the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton. In this work, we developed the hemisynthesis of trichodermin and trichodermol derivatives in order to evaluate their antimicrobial and cytotoxic activities and to study the chemo-modulation of their bioactivity. Some derivatives with a short chain at the C-4 position displayed selective antimicrobial activity against Candida albicans and they showed MIC values similar to those displayed by trichodermin. It is important to highlight the cytotoxic selectivity observed for compounds 9, 13, and 15, which presented average IC50 values of 2 μg/mL and were cytotoxic against tumorigenic cell line MCF-7 (breast carcinoma) and not against Fa2N4 (non-tumoral immortalized human hepatocytes).

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Secondary Metabolites with Cytotoxic Activities from Streptomyces sp. BM-8 Isolated from the Feces of Equusquagga

Molecules ◽

10.3390/molecules26247556 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7556

Author(s):

Shengsheng Lu ◽

Jianan Hu ◽

Xi Xie ◽

Runhong Zhou ◽

Fangfang Li ◽

...

Keyword(s):

Culture Broth ◽

Cytotoxic Activities ◽

Aliphatic Acid ◽

Streptomyces Sp ◽

Nuclear Magnetic Resonance Spectra ◽

Cancerous Cells ◽

Ht 29 ◽

Acid Compound ◽

Leu 7 ◽

Mcf 7

A new aliphatic acid, compound 1, together with six known metabolites, including nonactic acid (2), homononactic acid (3), ethyl homononactate (4), homononactylhomononactate (5), valinomycin (6), and cyclo-(Pro-Leu) (7), was isolated from the culture broth of Streptomyces sp. BM-8, an actinobacterial strain isolated from the feces of Equus quagga. The structures of these compounds were established by analyses of spectroscopic data, including 1D and 2D nuclear magnetic resonance spectra (NMR), as well as by HR-ESI-MS spectrometry and chemical derivative analyses. Additionally, a serial analogue of nonactic acid and homononacticacid (8–21) was synthesized. The cytotoxicity of 1–21 wastested against a panel of cancer cell lines, such as HT-29, MCF-7, A375 and K562, with MTT assay. In addition, the cytotoxicity tests revealed that 1 was less cytotoxic toward a panel of cancerous cells, as compared with valinomycin (6).

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Cytotoxic Activity of Some Spirooxindole-4H-pyran Derivatives

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2019/v31i630364 ◽

2019 ◽

pp. 1-6

Author(s):

Zeinab Faghih ◽

Zahra Faghih ◽

Masoomeh Divar ◽

Soghra Khabnadideh

Keyword(s):

Cell Line ◽

Cell Lines ◽

Anticancer Agents ◽

Biological Activities ◽

Science Research ◽

Cytotoxic Activities ◽

Medical Sciences ◽

Anticancer Properties ◽

Cancerous Cell ◽

Mcf 7

Aims: Isatin is a honored scaffold and one of the most favorable class of heterocyclic systems that possesses many interesting biological activities and well-tolerated in humans. Here a series of fifteen spirooxindole-4H-pyran derivatives containing both isatin and pyran moieties (ICa-ICo) will be examine for their anti-cancer activity. Study Design: Cytotoxic evaluation of some spirooxindole-4H-pyran derivatives in two cancerous cell lines. Place and Duration of Study: Pharmaceutical Science Research Center and Shiraz Institute for Cancer Research, Medical School in Shiraz University of Medical Sciences, Shiraz, Iran, between June 2018 and July 2019. Methodology: MTT assay was used to evaluate the cytotoxic activities of these compounds. The anticancer properties of the tested compounds were determined using A549 and MCF-7 cell lines. Results: Among the tested compounds ICc, ICd and ICf showed the best cytotoxic activities against both cancerous cell lines. Compounds ICh and ICj showed desirable cytotoxic activities against A549 cell line. Compound ICb showed desirable cytotoxic activities against MCF-7 cell line. Conclusion: We conclude that the isatin-linked pyran analog can serve as a prototype molecule for further development of a new class of anticancer agents.

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Evaluating Cytotoxic Potential of the Fruit and the Leaf Extracts of Sambucus ebulus (L.) on MCF7 and AGs Cell Lines

Research in Molecular Medicine ◽

10.32598/rmm.9.1.2 ◽

2021 ◽

Vol 9 (1) ◽

pp. 11-20

Author(s):

Farzaneh Rasouli Asl ◽

◽

Ali Barzegar ◽

Mohammad Ali Ebrahimzadeh ◽

◽

...

Keyword(s):

Cell Lines ◽

Cytotoxic Activities ◽

Cancer Therapies ◽

Leaf Extracts ◽

Ags Cells ◽

Sambucus Ebulus ◽

Ic50 Values ◽

Low Cytotoxicity ◽

Inhibitory Potential ◽

Mcf 7

Background: Breast and stomach cancers are the most common malignancies in Iranian females and males, respectively. Enriching with phytochemicals that have antioxidant and cytotoxic activities, extracts from dwarf elder (Sambucus ebulus L.) holds promises to be used for alternative medication. Materials and Methods: We investigated the cytotoxic and antiproliferative activities of the leaf and the fruit ethyl-acetate (EA), as well as the methanolic (MeOH) extracts of dwarf elder upon treatment of the MCF-7 and AGS cells. Twenty-seven concentration series ranging from 10 to 2000 μg/mL were administered to the cells, and their growth inhibitory potential was assessed using MTT assay. The potential anticancer compounds of the extracts were quantified applying an improved highperformance liquid chromatography (HPLC). Results: All extracts showed positive dose-dependent cytotoxic activities on both cell lines. The EA extracts demonstrated more cytotoxicity compared to those of the MeOH ones (P<0.0001). The leaf EA extract showed IC50 values of 65 and 50 μg/mL, while those of the fruit were estimated as 58 and 50 μg/mL on the MCF-7 and AGS cells, respectively. The AGS cell line showed more susceptibility to all extracts tested compared to the MCF-7. MeOH extracts caused only a maximum of ~20% reduction in cell viability at 2000 μg/mL concentration. According to the HPLC analysis, leaf extracts contained phenolic compounds, including p- coumaric acid (0.10 mg per g powder), rutin (0.07 mg per g powder), and quercetin (0.02 mg per g powder). Conclusion: EA extract of the fruit shows the highest cytotoxicity: reducing 35.3% viability of the AGS cells with 10 μg/mL concentration. It can be considered a potential chemopreventive agent for cancer therapies. However, MeOH extracts with far low cytotoxicity or non-cytotoxic at some concentrations would be an appropriate candidate for preventing tumor growth without affecting neighboring normal cells.

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