New chalcone-type compounds and 2-pyrazoline derivatives: synthesis and caspase-dependent anticancer activity

2020 ◽  
Vol 12 (6) ◽  
pp. 493-509 ◽  
Author(s):  
Mohamed I Chouiter ◽  
Houssem Boulebd ◽  
David M Pereira ◽  
Patrícia Valentão ◽  
Paula B Andrade ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Human Lung ◽  
Human Lung Fibroblast ◽  
Regulated Cell Death ◽  
Ags Cell Line ◽  
Novel Structures

Aim: There is a continuous and urgent need for new anticancer agents with novel structures and target selectivity. Methods & results: The anticancer activity of the prepared compounds was assessed against human lung (A549) and stomach (AGS) cancer cell lines and evaluated in the noncancer human lung fibroblast (MRC-5) cell line. 2-Pyrazolines were devoid of toxicity in all cell lines used, chalcones bearing a β-(benz)imidazole moiety being toxic toward AGS cell line. Mechanistic studies showed that these compounds trigger loss of cell viability and mitochondrial membrane potential, while eliciting morphological traits compatible with regulated cell death, which was ultimately shown to derive from caspase activation, specifically caspase-3. Conclusion: Chalcones 1–3 have been identified as new and promising anticancer agents toward the AGS cell line.

scholarly journals Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6305
Author(s):  
Abdullah Mohammed Al-Majid ◽  
M. Ali ◽  
Mohammad Shahidul Islam ◽  
Saeed Alshahrani ◽  
Abdullah Saleh Alamary ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Stereoselective Synthesis ◽  
Cancer Cell Lines ◽  
Azomethine Ylides ◽  
Active Member ◽  
One Pot

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC50 = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC50 = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO2 substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC50 = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.

scholarly journals In vitro Anticancer Activity of Marine Sponges Against T47D and HeLa Cell Lines

2020 ◽  
Vol 19 (1) ◽  
pp. 25-28
Author(s):  
Suciati ◽  
Lusiana Arifianti
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Marine Sponges ◽  
Hela Cell Lines

Marine sponges have been known as the source of natural products. Various metabolites with potent bioactivities have been reported from this organism. The current study aims to investigate the anticancer potency of three marine sponges namely Diacarnus debeauforti, Haliclona amboinensis and Agelas cavernosa collected from Barrang Lompo Island, South Sulawesi, Indonesia. The ethyl acetate extracts of the sponges were screened against T47D breast cancer cells and HeLa cervical cancer cells by using the MTT method. The results showed that these sponges demonstrated anticancer activity against both cancer cell lines. The lowest IC50 of 18.2 μg/ml was given by the extract of A. cavernosa against T47D cell line, while in the screening against HeLa cancer cell line, the extract of D. debeauforti revealed the highest potency with IC50 of 15.7 μg/ml. Our results suggested that the marine sponges namely D. debeauforti, H. amboinensis and A. cavernosa can be good candidates for the development of anticancer agents. Dhaka Univ. J. Pharm. Sci. 19(1): 25-28, 2020 (June)

Bacterial Biotransformation and Anticancer Activities of Betulin against A549, HepG2 and 5RP7 Cancer Cell Lines

2020 ◽  
Vol 20 ◽  
Author(s):  
İsmail Kıran ◽  
Gülşen A. Çiftçi ◽  
Özlem A. Eklioğlu ◽  
Şaziye G.K. Akkaya
Keyword(s):  
Cell Cycle ◽  
Staphylococcus Aureus ◽  
Membrane Potential ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Anticancer Activities ◽  
Cycle Arrest

Background: A pentacyclic lupenane-type natural triterpenoid, betulin, has attracted attention in medicinal chemistry since it exhibited a variety of biological activities including anticancer activity. Objective: In the present work, it was aimed to obtain derivatives of betulin through bacterial biotransformation and investigate its anticancer activity against A549, HepG2 and 5RP7 cancer cell lines. Methods: Bacterial biotransformation studies were continued in a MBH broth medium for 7 days at 35oC. Anticancer activities of betulin against A549, HepG2 and 5RP7 cell lines were carried out using XTT assay and their selectivity was determined using healthy cell line of NIH/3T3. Cell proliferation ELISA, BRDU (colorimetric) assay was used for measuring proliferation in replicative cells in which DNA synthesis occurs. Flow cytometric analysis was used for measuring apoptotic cell percentages, caspase 3 activation and mitochondrial membrane potential. Results: Bacterial biotransformation studies with 7 bacteria of Staphylococcus aureus ATCC 6538, Proteus vulgaris NRRL B-123, Bacillus subtilis NRRL B-4378, Streptomyces griseolus NRRL B-1062, Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 43300 and Bacillus velezensis NRRL B-14580 produced no metabolite. In in vitro anticancer activity studies, betuline was found to exert anticancer activity against A549, HepG2 and 5RP7 cell lines with an IC50 values of 207.7, 125.0 and 28.3 µg/mL whereas SI values were found to be 30, 50 and 223, respectively. Early and late apoptotic percentages of betulin were found as 9.6, 12.1 and 85.4 % on A549, HepG2 and 5RP7, respectively, while caspase 3 positive cell percentages were 2.3, 28.7 and 13.3 % for IC50 concentrations. In addition, betulin caused G1 cell cycle arrest (49.5 %) on 5RP7 cell line. Conclusion: The results have been shown that betulin activities against A549 and HepG2 cell lines were nonselective and limited its cyctotoxic activity against healthy cells but it is possible to say that it exerted selective activity against 5RP7 cell (28.33±1.53 µg/mL). Betulin effects on apoptosis was found to be dose-dependent while its effect on caspase 3 activation, mitochondrial membrane potential and cell cycle arrest on G0/G1 phase were not dependent on doses. Therefore, betulin could be a good canditate for the treatment of H-ras active cancer types.

scholarly journals Synergistic activity of Hsp90 inhibitors and anticancer agents in pancreatic cancer cell cultures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Simonas Daunys ◽  
Daumantas Matulis ◽  
Vilma Petrikaitė
Keyword(s):  
Pancreatic Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Anticancer Agents ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Synergistic Activity

Abstract Heat shock protein 90 (Hsp90) is a widely investigated target for anticancer therapy. The experimental Hsp90 inhibitors ICPD47 and ICPD62 demonstrated anticancer activity against colorectal, osteosarcoma and cervical cancer cell lines. However, their anticancer activity has not been investigated against pancreatic cancer cell lines yet, and there are no data about synergistic activity of these compounds in combination with clinically used anticancer agents. Pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 were exposed to ICPD47 and ICPD62 alone and in combinations with antimetabolites gemcitabine (GEM), 5-fluorouracil (5-FU) and topoisomerase inhibitor doxorubicin (DOX). Effects on cell viability were determined by MTT assay. The synergistic activity was evaluated using Chou-Talalay method. Also, 3D cell cultures were formed using 3D Bioprinting method and the activity of each compound and their combinations was examined by measuring the size change of spheroids. The strongest synergistic activities were determined in combinations using all ratios of ICPD47 with GEM and ICPD62 with GEM in MIA PaCa-2 cell line (combination index <0.5). The combinations of ICPD47 with 5-FU and ICPD47 with GEM in a ratio of 1:5 showed the greatest effect on tumour spheroid growth in both cell lines. The ICPD47 in combination with mild hyperthermia showed significant results, where the EC50 value in PANC-1 cell line dropped from 4.04 ± 0.046 to 1.68 ± 0.004 µM. The ICPD47 and ICPD62 under the same conditions could act synergistically with GEM, 5-FU and DOX and is worth of further investigations, and studies of synergistic effect is a promising path for more efficient anticancer therapies.

scholarly journals The Potential of Dietary Antioxidants from a Series of Plant Extracts as Anticancer Agents against Melanoma, Glioblastoma, and Breast Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1115
Author(s):  
Mindaugas Liaudanskas ◽  
Vaidotas Žvikas ◽  
Vilma Petrikaitė
Keyword(s):  
Breast Cancer ◽  
Antioxidant Activity ◽  
Phenolic Compounds ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Plant Extracts ◽  
Anticancer Agents ◽  
Leaf Extract

In modern society, cancer is one of the most relevant medical problems. It is important to search for promising plant raw materials whose extracts have strong antioxidant and anticancer effects. The aim of this study was to determine the composition of phenolic compounds in plant extracts, to evaluate their antioxidant and anticancer activity, and to find the correlations between those activities. Extracts of calendula, sage, bearberry, eucalyptus, yarrow, and apple were selected for the study. The phenolic compounds of these extracts were determined by the UPLC-ESI-MS/MS method and the antioxidant activity was evaluated in vitro by four different UV-VIS spectrophotometric methods (ABTS, DPPH, CUPRAC, FRAP). The anticancer activity of extracts was tested against melanoma IGR39, glioblastoma U-87, and triple-negative breast cancer MDA-MB-231 cell lines in vitro by MTT assay. The highest content of identified and quantified phenolic compounds was found in sage leaf extract and the lowest in ethanol eucalyptus leaf extract. The highest antioxidant activity was determined by all applied methods for the acetone eucalyptus leaf extract. The majority of extracts were mostly active against the melanoma IGR39 cell line, and possessed the lowest activity against the glioblastoma U-87 cell line. Acetone extract of eucalyptus leaf samples exhibited the highest anticancer activity against all tested cell lines. Strong and reliable correlation has been found between antioxidant and anticancer activity in breast cancer and glioblastoma cell lines, especially when evaluating antioxidant activity by the FRAP method.

Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

2020 ◽  
Vol 17 (10) ◽  
pp. 772-778
Author(s):  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Yahya I. Asiri ◽  
Jaber Abdullah Alshehri ◽  
Yahia N. Mabkhot ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Mode ◽  
Docking Studies ◽  
Solvent Free ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Solvent Free Conditions ◽  
Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Human Lung Fibroblast ◽  
Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction

2019 ◽  
Vol 18 (15) ◽  
pp. 2124-2130
Author(s):  
Amany Belal
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Assay Method ◽  
Breast Adenocarcinoma ◽  
Compound I ◽  
Design Synthesis ◽  
Ic50 Values ◽  
New Compounds

Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized. Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method. Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds). Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.

scholarly journals Bimetallic Iron–Palladium Catalyst System as a Lewis-Acid for the Synthesis of Novel Pharmacophores Based Indole Scaffold as Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2212
Author(s):  
Mohammad Shahidul Islam ◽  
M. Ali ◽  
Abdullah Mohammed Al-Majid ◽  
Abdullah Saleh Alamary ◽  
Saeed Alshahrani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Palladium Catalyst ◽  
Cancer Cell Line ◽  
Catalyst System ◽  
Mcf 7 ◽  
Iron Palladium

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC50 values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC50 = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC50 = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC50 = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.

scholarly journals Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Design And Synthesis ◽  
Human Breast Cell ◽  
Mcf 7

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.

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