scholarly journals Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohammed Hawash ◽  
Deniz Cansen Kahraman ◽  
Sezen Guntekin Ergun ◽  
Rengul Cetin-Atalay ◽  
Sultan Nacak Baytas
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Anticancer Activities ◽  
Element Analysis ◽  
Chemical Structures ◽  
Huh7 Cells

Abstract Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, 1H-NMR and 13C-NMR spectroscopy and element analysis. Results The cytotoxic activity was performed against Huh7, MCF7 and HCT116 cancer cell lines using sulforhodamine B assay. Some compounds showed potent anticancer activities and three of them were chosen for further evaluation on liver cancer cell lines based on SRB assay and real-time cell growth tracking analysis. Compounds were shown to cause arrest in the G0/G1 phase in Huh7 cells and caused a significant decrease in CDK4 levels. A good correlation was obtained between the theoretical predictions of bioavailability using Molinspiration calculation, Lipinski’s rule of five, and experimental verification. These investigations reveal that indole-isoxazole hybrid system have the potential for the development of novel anticancer agents. Conclusions This study has provided data that will form the basis of further studies that aim to optimize both the design and synthesis of novel compounds that have higher anticancer activities.

scholarly journals Cytotoxic activities of synthesized curcumin and 3,4-Difluorinated curcumin against HepG2, LU-1 and KB cancer cell lines

2020 ◽  
Vol 23 (4) ◽  
pp. 781-787
Author(s):  
Nhan Phuoc Hoai Phan ◽  
Van Thi Bich Pham ◽  
Tu Dang Quoi Phan ◽  
Tuyen Nguyen Kim Pham ◽  
Hao Minh Hoang
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Aldol Condensation ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Coupling Reactions ◽  
Anticancer Activities ◽  
Chemical Structures ◽  
Curcumin Analogues ◽  
Michael Acceptors

Introduction: Natural curcuminoids isolated from turmeric (Curcuma longa L.) have been limited in number and the amount of substrates evaluated in semi-synthetic processes and biological tests. Currently, potent anticancer activities of curcuminoids have garnered increased attention such that a greater number of synthetic procedures of curcumin analogues have been developed for further biological evaluations. The fluorine substituent of fluorinated compounds is important for biological responses. However, natural products bearing fluorine have rarely been found. In the study herein, we employed an aldol condensation between 4-hydroxy-3-methoxybenzaldehyde/3,4- difluorobenzaldehyde and pentane-2,4-dione to synthesize the desired curcumin (Cur) and 3,4- difluorinated curcumin (3,4-DFCur). Their half-maximal inhibitory concentration (IC50) values against HepG2, LU-1 and KB cancer cell lines were then assessed. Methods: Pentane-2,4-dione was converted to enol form by using B2O3 before carrying out C-C coupling reactions with benzaldehyde analogues under basic conditions. The water scavenger was added to the reaction to capture the produced water. The reaction mixture was stirred at 70 ◦C. The reaction progress was monitored by thin layer chromatography (TLC). Crude products were purified by flash column chromatography (CC; SiO2, eluent: HEX/EA = 9/1!7/3). The chemical structures of the desired products were elucidated by 1H, 13C-NMR, HSQC and MS spectra. The anticancer activities of Cur and 3,4- DFCur against HepG2, LU-1 and KB cancer cell lines were determined using MTT method. Results: Under reasonable reaction conditions, the yields for the coupling reactions were 53 and 72% for Cur and 3,4-DFCur, respectively. The stable enol tautomer of 1,3-diketone and the trans-configuration in a seven-carbon chain of product skeletons were assigned by 1H-NMR spectra. All synthesized products showed anticancer activities, with Cur exhibiting higher inhibitory activities when compared with 3,4-DFCur. Cur and 3,4-DFCur are Michael Acceptors; their cytotoxic activities could be attributed to the inhibition of glutathione S-transferase, a detoxification enzyme, by forming glutathionyl adducts. The decreased inhibitory capacities of 3,4-DFCur were due to the effect of fluorine which results in the unfavorable formation of reactive radicals and an increase in lipophilicity. Conclusions: Curcumin and 3,4-difluorinated curcumin were completely synthesized in 53% and 72% yields. The synthetic procedure is applicable for synthesizing curcumin derivatives bearing various substituents on the aromatic rings, i.e., not limited to methoxy (-OCH3) and hydroxy (- OH) groups. Unexpectedly, the presence of fluorines in 3,4-DFCur led to lower cytotoxic activities against cancer cell lines. Our results provide greater insight on the structure-activity relationship of curcumin analogues against cancer cell lines.

scholarly journals Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 40
Author(s):  
Hatice Bekci ◽  
Mustafa Cam ◽  
Ahmet Cumaoglu
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM).

Anticancer Activity of Novel Platinum Complex as DNA Binders

2013 ◽  
Vol 781-784 ◽  
pp. 1107-1110
Author(s):  
Xu Jian Luo ◽  
Qi Pin Qin ◽  
Yu Lan Li ◽  
Yan Cheng Liu
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Normal Cell ◽  
Platinum Complex ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Element Analysis ◽  
Normal Cells ◽  
Dna Binders ◽  
Ct Dna

A new phenanthroimidazole platinum (II) complex has been synthesized and characterized by IR, NMR, ESI-MS, element analysis. The affinities of the complex toward ct-DNA was determined by circular dichroism absorption (CD), UV-Vis absorption. Results indicate that the complex interact with ct-DNA by classical intercalating mode. The cytotoxicities of the complex was screened against four cancer cell lines and normal cells of HL-7702 in comparison to cisplatin and it showed a higher activity than cisplatin, with IC50 values in the range 8.7417.11 μmol/L. Furthermore, the complex displayed lower cytotoxic activities to HL-7702 (normal cell) compared with the cancer cell lines.

scholarly journals Design and Evaluation of Licochalcone A Derivatives as Anticancer Agents

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300
Author(s):  
Goo Yoon ◽  
Seung Hoon Cheon ◽  
Jung Hyun Shim ◽  
Seung Sik Cho
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Licochalcone A ◽  
Lead Compounds ◽  
Further Development ◽  
Derivatives Of

New derivatives of licochalcone A were synthesized and evaluated for their potential anticancer activities. Compounds 6 (( E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxy phenyl) acryloyl) phenyl)-4-isopropylbenzamide) and 8 (1-(3-dimethylamino-phenyl)-3-(2-trifluoromethyl-phenyl)-propenone) showed potent activity against the screened cancer cell lines with that of compound 6 ranging from 6.9 ± 0.2 μM to 22.9 ± 3.1 μM, and that of compound 8 from 4.2 ± 0.5 μM to 11.8 ± 0.7 μM. Both compounds showed stronger cytotoxicity than that of licochalcone A. These two candidates have very different substituents and could be considered as promising lead compounds for further development of potent anticancer agents.

scholarly journals Design, Synthesis, In Vitro Anticancer Evaluation and Molecular Modelling Studies of 3,4,5-Trimethoxyphenyl-Based Derivatives as Dual EGFR/HDAC Hybrid Inhibitors

2021 ◽  
Vol 14 (11) ◽  
pp. 1177
Author(s):  
Tarek S. Ibrahim ◽  
Azizah M. Malebari ◽  
Mamdouh F. A. Mohamed
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Hydroxamic Acid ◽  
Phenyl Group ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Molecular Docking Study

Recently, combining histone deacetylase (HDAC) inhibitors with chemotherapeutic drugs or agents, in particular epidermal growth factor receptor (EGFR) inhibitors, is considered to be one of the most encouraging strategy to enhance the efficacy of the antineoplastic agents and decrease or avoid drug resistance. Therefore, in this work, based on introducing 3,4,5-trimethoxy phenyl group as a part of the CAP moiety, in addition to incorporating 4–6 aliphatic carbons linker and using COOH or hydroxamic acid as ZBG, 12 novel EGFR/HDAC hybrid inhibitors 2a–c, 3a–c, 4a–c and 5a–c were designed, constructed, and evaluated for their anticancer activities against 4 cancer cell lines (HepG2, MCF-7, HCT116 and A549). Among all, hybrids with hydroxamic acid 4a–c and 5a, exhibited the highest inhibition against all cancer cell lines with IC50 ranging from 0.536 to 4.892 μM compared to Vorinostat (SAHA) with IC50 ranging from 2.43 to 3.63 μM and Gefitinib with IC50 ranging from 1.439 to 3.366 μM. Mechanistically, the most potent hybrids 4a–c and 5a were further tested for their EGFR and HDACs inhibitory activities. The findings disclosed that hybrid 4b displayed IC50 = 0.063 µM on the target EGFR enzyme which is slightly less potent than the standard Staurosporine (IC50 = 0.044 µM). Furthermore, hybrid 4b showed less HDAC inhibitory activity IC50 against HDAC1 (0.148), 2 (0.168), 4 (5.852), 6 (0.06) and 8 (2.257) than SAHA. In addition, the investigation of apoptotic action of the most potent hybrid 4b showed a significant increase in Bax level up to 3.75-folds, with down-regulation in Bcl2 to 0.42-fold, compared to the control. Furthermore, hybrid 4b displayed an increase in the levels of Caspases 3 and 8 by 5.1 and 3.15 folds, respectively. Additionally, the cell cycle analysis of hybrid 4b revealed that it showed programmed cell death and cell cycle arrest at G1/S phase. Moreover, all these outcomes together with the molecular docking study recommended the rationalized target hybrids 4a–c and 5a, particularly 4b, may be considered to be promising lead candidates for discovery of novel anticancer agents via dual inhibition of both EGFR/HDAC enzymes.

scholarly journals Streptomyces griseus KJ623766: A Natural Producer of Two Anthracycline Cytotoxic Metabolites β- and γ-Rhodomycinone

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4009
Author(s):  
Ahmed S. Abu Zaid ◽  
Ahmed E. Aleissawy ◽  
Ibrahim S. Yahia ◽  
Mahmoud A. Yassien ◽  
Nadia A. Hassouna ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ethyl Acetate Extract ◽  
Biological Activities ◽  
Streptomyces Griseus ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Chemical Structures ◽  
Bioassay Guided Fractionation

Background: This study aimed to produce, purify, structurally elucidate, and explore the biological activities of metabolites produced by Streptomyces (S.) griseus isolate KJ623766, a recovered soil bacterium previously screened in our lab that showed promising cytotoxic activities against various cancer cell lines. Methods: Production of cytotoxic metabolites from S. griseus isolate KJ623766 was carried out in a 14L laboratory fermenter under specified optimum conditions. Using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide assay, the cytotoxic activity of the ethyl acetate extract against Caco2 and Hela cancer cell lines was determined. Bioassay-guided fractionation of the ethyl acetate extract using different chromatographic techniques was used for cytotoxic metabolite purification. Chemical structures of the purified metabolites were identified using mass, 1D, and 2D NMR spectroscopic analysis. Results: Bioassay-guided fractionation of the ethyl acetate extract led to the purification of two cytotoxic metabolites, R1 and R2, of reproducible amounts of 5 and 1.5 mg/L, respectively. The structures of R1 and R2 metabolites were identified as β- and γ-rhodomycinone with CD50 of 6.3, 9.45, 64.8 and 9.11, 9.35, 67.3 µg/mL against Caco2, Hela and Vero cell lines, respectively. Values were comparable to those of the positive control doxorubicin. Conclusions: This is the first report about the production of β- and γ-rhodomycinone, two important scaffolds for synthesis of anticancer drugs, from S. griseus.

Recent development of tetrahydro-quinoline/isoquinoline based compounds as anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratik Yadav ◽  
Ashish Kumar ◽  
Ismail Althagafi ◽  
Vishal Nemaysh ◽  
Reeta Rai ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Cancer Cell Lines ◽  
New Drugs ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Anticancer Properties

: Tetrahydroquinoline and isoquinoline scaffolds are important class heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinolines based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wide-ranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.

Evaluation of Cytotoxic Potentials of Some Isoindole-1, 3-Dione Derivatives on HeLa, C6 and A549 Cancer Cell Lines

2020 ◽  
Vol 16 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Ayse Tan ◽  
Ayse Sahin Yaglioglu ◽  
Nurhan Horasan Kishali ◽  
Ertan Sahin ◽  
Yunus Kara
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
In Vivo Studies ◽  
Silyl Ether ◽  
Anticancer Activities ◽  
Alkyl Aryl ◽  
Starting Compound

Objective: Considering this information, firstly, isoindole derivatives containing different functional groups 4-13 have been synthesized from 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole-1, 3(2H)-dione. Background: Norcantharimides are known as norcantharidine derivatives and contain an isoindole skeleton structure. Isoindole derivatives have positive effect on inflammatory pathologies including cancers. Methods: For the synthesis of all compounds, 2-alkyl/aryl-3a, 4,7,7a-tetrahydro-1H-isoindole- 1,3(2H)-dione was used as the starting compound. The syntheses were based on two main reactions: Ene-reaction of singlet oxygen and epoxidation. Secondly, their anticancer activities were evaluated against HeLa, C6 and A549 cancer cell lines by the BrdU assay. Results: Anticancer activities of synthesized compounds (4-13) and 5-FU (5-Florouracil) against HeLa, C6 and A549 cells were investigated at four concentrations (100, 50, 25 and 5 μM). IC50 values of compounds 4-13 were calculated for all cancer cell lines. The investigated compounds showed anticancer activity against the cancer cell lines depending on doses. Compound 7 containing azide and silyl ether exhibited higher inhibitory activity than the other compounds and 5-FU against A549 cancer cell lines (IC50 =19.41± 0.01 μM). Compounds 9 and 11 were determined to exhibit cell-selective activity against HeLa cancer cell lines. Compound 11 had higher activity than the positive control at 100 μM concentrations against C6 cancer cell lines. Conclusion: According to the results observed, isoindole derivatives 7, 9, and 11 might be good potential anticancer agents for the treatment of cervical and glioma cancer due to their antiproliferative properties, having less cytotoxic effects on healthy cells. In addition, compound 7 could be used in in vivo studies of all three-cancer cell lines (C6, HeLa, and A549).

Design, Synthesis and Biological Evaluation of a Novel Series of Indole-3- Carboxamide Derivatives for Cancer Treatment as EGFR Inhibitors

2018 ◽  
Vol 15 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Lan Zhang ◽  
Xin-Shan Deng ◽  
Guang-Peng Meng ◽  
Chao Zhang ◽  
Cong-Chong Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Egfr Inhibitors ◽  
Target Compound ◽  
Anticancer Activities ◽  
Aberrant Expression

Background: As reported EGFR is a sialoglycoprotein with tyrosine kinase activity involved in control of cellular survival, multiplication, differentiation and metastasis. Dysregulation or aberrant expression of EGFR has been implicated in cell transformation and having oncogenic roles in a number of human cancers. Therefore EGFR has become a significant target for developing targeted therapy for cancer. Methods: A novel series of indole-3-carboxamide derivatives as EGFR inhibitors were designed, synthesized and evaluated for the anticancer activity in vitro against three EGFR high-expressed cancer cell lines (A549, HeLa, and SW480), one EGFR low-expressed cell line (HepG2) and one human liver normal cell line (HL7702) by MTT assay. Results: The target compounds 6c, 6f, 6i, 6j, 6l, 6r, 6u and 6x exhibited potent anticancer activities against the three tested cancer cell lines and weak cytotoxic effects on HepG2, which imply that the target compounds are probably effective in inhibiting EGFR. And they also did not show measurable activities in HL7702, which imply the target compounds are likely to overcome the nonspecific toxicity against normal cells. Particularly, the target compound 6x indicated equal to the positive control erlotinib. In addition, molecular docking studies demonstrated the target compound 6x may be the potential inhibitor to EGFR. Conclusion: A new EGFR inhibitor scaffold and a preliminary discussion on their SARs provide promising opportunities to guide further research on indole-3-carboxamide derivatives as novel anticancer agents.

Detection of natural inhibitors against human liver cancer cell lines through QSAR, Molecular Docking, and ADMET studies

2020 ◽  
Vol 20 ◽  
Author(s):  
Sarfaraz Alam ◽  
Sadaf Nasreen ◽  
Ateeque Ahmad ◽  
Mahendra Pandurang Darokar ◽  
Feroz Khan
Keyword(s):  
Liver Cancer ◽  
High Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Liver Cancer Cell ◽  
Qsar Study ◽  
Lab Experiments ◽  
Wet Lab

Background: Liver cancer is ranked as the fifth most prevalent and third most lethal cancer worldwide. The incidence rates of this cancer are on the rise, and only limited treatment options are available. Methods: To identify and optimize the inhibitors of liver cancer cell-lines, a QSAR model was developed by using multiple linear regression methods. The robustness of the model was validated through statistical methods and wet-lab experiments. Results: The developed QSAR models yielded high activity descriptor relationship accuracy of 91%, referred by regression coefficient (r2= 0.91), and a high activity prediction accuracy of 89%. The external predicted (pred_r2 ) ability of the model was 90%. Conclusion: The QSAR study indicates that chemical descriptors such as to measure of electronegative atom count (Epsilon3), atom type count descriptors (MMFF_10), number of a carbon atom connected with four single bonds (SssssCEindex), molecular weight and, number of oxygen atom connected with two aromatic bonds (SaaOE-index) are significantly correlated with anticancer activity. The model, which was validated statistically and through wet-lab experiments, was further used in virtual screening of potential inhibitors against the liver cancer cell line WRL68. ADMET risk screening, synthetic accessibility, and Lipinski's rule of five are used to filter false positive hits. Afterward, to achieve a set of aligned ligand poses and rank the predicted active compounds, docking studies were carried out. The studied compounds and their metabolites were also analyzed for different pharmacokinetics parameters. Finally, a series of compounds were proposed as anticancer agents.

Sign in / Sign up

Export Citation Format

Share Document