Design, Synthesis and Anticancer Activity of New Thiazole-Tetrazole or Triazole Hybrid Glycosides Targeting CDK-2 via Structure-Based Virtual Screening

2019 ◽  
Vol 19 (11) ◽  
pp. 933-948 ◽  
Author(s):  
Asmaa F. Kassem ◽  
Eman M. H. Abbas ◽  
Dina S. El-Kady ◽  
Hanem M. Awad ◽  
Wael A. El-Sayed
Keyword(s):  
Anticancer Activity ◽  
Cycloaddition Reaction ◽  
Molecular Surface ◽  
Dipolar Cycloaddition ◽  
Breast Adenocarcinoma ◽  
Cyclin Dependent Kinase ◽  
Design Synthesis ◽  
Adenocarcinoma Cells ◽  
Ic50 Values ◽  
Epithelium Cells

Background & Objective: The target tetrazole glycosides were synthesized by construction of ring system by cycloaddition reaction of benzothiazole-linked nitrile derivative and sodium azide followed by N-glycosylation process and deprotection. Methods: The triazole glycosides were prepared by applying click approach involving dipolar cycloaddition of benzothiazole possessing alkyne functionality and different glycosyl azides. The products incorporating acyclic analogs of sugar moieties were synthesized through alkylation using acyclic oxygenated halides. Results: The anticancer activity was studied against human breast adenocarcinoma cells (MCF-7) and human normal Retina pigmented epithelium cells (RPE-1). High activities were revealed by three compounds with IC50 values 11.9-16.5 µM compared to doxorubicin (18.6 µM) in addition to other four derivatives with good inhibition activities. Conclusion: Enzyme docking investigation was performed into cyclin-dependent kinase 2 (CDK2); a potential target for cancer medication. Compounds which have possessed highest activities revealed good fitting inside the binding site of the protein molecular surface and showed minimum binding energy.

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.

Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

2021 ◽  
Vol 21 ◽  
Author(s):  
Nishtha Shalmali ◽  
Sandhya Bawa ◽  
Md Rahmat Ali ◽  
Sourav Kalra ◽  
Raj Kumar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Active Sites ◽  
Colorectal Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Adenocarcinoma Cells ◽  
Ic50 Values

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines. Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity. Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme-Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified. Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 µM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 µM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 µM and 106.91 µM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores -9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five. Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

scholarly journals Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4388 ◽  
Author(s):  
Morak-Młodawska ◽  
Pluta ◽  
Latocha ◽  
Jeleń ◽  
Kuśmierz
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Fibroblasts ◽  
Human Tumor ◽  
Design Synthesis ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Normal Human ◽  
Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

scholarly journals Green synthesis of silver nanoparticles by Aspergillus consortium and evaluating its anticancer activity against Human breast adenocarcinoma cell line (MCF7)

2017 ◽  
Vol 4 (1) ◽  
pp. 28 ◽  
Author(s):  
Rajeswari P. ◽  
Samuel P. ◽  
Vijayakumar J. ◽  
Selvarathinam T. ◽  
Sudarmani D.N.P. ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Anticancer Activity ◽  
Cell Line ◽  
Tamil Nadu ◽  
Breast Adenocarcinoma ◽  
Metallic Silver ◽  
Ic50 Values ◽  
Mcf7 Cell Line ◽  
Ft Ir ◽  
Cell Inhibition

Objective: The objective of the present study is to produce silver nanoparticles from marine fungi from south west coastal areas of Tamil Nadu and evaluating their potentials with special reference to anticancer activity.Methods: Hand core pushing technique is adapted to collect marine sediment samples along the coastal environs. Distinguished Aspergillus colonies were isolated and identified by wet mount procedure. The characterized Aspergillus consortium was subjected to produce silver nanoparticles. The extracellularly synthesized nanoparticles were characterized. Silver nanoparticles were evaluated for anticancer activity against MCF7 cell line by MTT assay. The IC50 values were determined.Results: Aspergillus consortium consist of A. niger, A. michelle and A. japonicus. Silver nanoparticles were extracellularly synthesized by the reduction of silver nitrate (AgNO3) to metallic silver (Ag+) ions results in the transformation of pale yellow to dark red colour. Constant shift was observed at 420 nm while monitoring the solution by UV-Vis spectrophotometer. The presence of important functional groups like –NH3 was confirmed by FT-IR Spectroscopy. Anticancer activity of the silver nanoparticles was evaluated against MCF7. There was 100% cell inhibition when concentration of the AgNPs reached 25 µg, 50 µg and 100 µg respectively in the test solution. Notably the IC50 value was found to be very lowest for the nanoparticles produced by A. japonicus and the value was found to be 1.47 µg/ml.Conclusions: Aspergillus consortium was found to be an ideal mycobiosystem for the production of silver nanoparticles with potential anticancer activity.

DESIGN, SYNTHESIS AND EVALUATION OF 6-SUBSTITUTED-4-HYDROXY-1-(2- SUBSTITUTEDACETYL)-3-NITROQUINOLIN-2(1H)-ONES FOR ANTICANCER ACTIVITY

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (12) ◽  
pp. 20-27
Author(s):  
S. S Bhat ◽  
◽  
S. N. MamleDesai ◽  
V. Narvekar ◽  
S. G Shingade ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Docking Study ◽  
The Other ◽  
Secondary Amines ◽  
Chloroacetyl Chloride ◽  
Design Synthesis ◽  
Mass Spectral ◽  
Ic50 Values ◽  
Substituted 1

The present work deals with the synthesis of a series of 6-substituted-4-hydroxy-1-(2-substitued alicyclicaminoacetyl)-3-nitroquinolin-2(1H)-one {IVa-d (1-3)} derivatives and evaluation of their in vitro anticancer activity. Docking study was carried out using EGFR-tyrosine kinase binding site (PDB ID: 1m17) and revealed encouraging results. The sequence of reactions consists of the initial synthesis of 6-substituted 4-hydroxyquinolin-2(1H)-ones (Ia-d), which were further subjected to nitration reaction to give 6- substituted-4-hydroxy-3-nitroquinolin-2(1H)-one (IIa-d). Condensation of compounds (IIa-d) with chloroacetyl chloride resulted in 6-substituted-1-(2-chloroacetyl)-4-hydroxy-3-nitroquinolin-2(1H)-one(IIIa-d), which was subjected to substitution reaction using various secondary amines to yield the title compounds {IVa-d (1-3)}. All the synthesized compounds were characterized by IR, NMR and mass spectral data.All the derivatives were tested for their in vitro anticancer activity using KB (oral cancer) cell lines. Among the synthesized compounds, compound (IVc-2) was found to be the most cytotoxic as compared to the other synthesized derivatives, with IC50 values of 0.2406μM/mL against KB cell line.

Synthesis of a Novel Series of 1,2,3-Triazole-Containing Artemisinin Dimers with Potent Anticancer Activity Involving Huisgen 1,3-Dipolar Cycloaddition Reaction

Synthesis ◽  
2011 ◽  
Vol 2011 (19) ◽  
pp. 3173-3179 ◽  
Author(s):  
Nabin Barua ◽  
Bishwajit Saikia ◽  
Partha Saikia ◽  
Abhishek Goswami ◽  
Ajit Saxena ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cycloaddition Reaction ◽  
Dipolar Cycloaddition

Design, Synthesis and Evaluation of Hybrid 2-Heteroaryl BenzimidazoleChalcone Derivatives as Anticancer Agents

2020 ◽  
Vol 17 ◽  
Author(s):  
Gajula Shyam Kumar ◽  
Bethi Rathnakar ◽  
Sridhar Gattu ◽  
Surender Singh Jadav ◽  
Nimma Rameshwar ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Phenyl Ring ◽  
Human Breast ◽  
Design Synthesis ◽  
Abl Tyrosine Kinase ◽  
Ovarian Cancer Cell Lines ◽  
Methoxy Groups ◽  
Ic50 Values ◽  
Human Breast Carcinoma Cells

: A series of 2-heteroaryl benzimidazole-chalcone hybrids were synthesized and the anticancer activity was estimated by MTT assay in human breast, lung, colon, and ovarian cancer cell lines. The biological results indicate that the compounds showed good anticancer activity with a range of IC50 values 0.056-19.5 µM. Compound 11b with hexa methoxy groups, bearing three methoxy groups on each terminal aryl ring exhibited a significant IC50 value (56 nM) against human breast carcinoma cells, which is 37 times higher potency in comparison with the reference Etoposide. Further compounds substituted variably with methoxy and nitro groups on the phenyl ring of chalcone showed more promising anticancer activity than the compounds with unsubstituted phenyl ring or variably alkyl-substituted phenyl ring of chalcone. The molecular docking results indicate that the synthesized compounds bind in the active site of Abl tyrosine kinase, the target of anticancer drug Imatinib. The present study provides the synergistic effect of hybrids, benzimidazole-chalcones as potential anticancer agents and will aid in the discovery of new anticancer agents.

Mitochondrial-dependent anticancer activity of δ-tocotrienol and its synthetic derivatives in HER-2/neu overexpressing breast adenocarcinoma cells

BioFactors ◽  
2013 ◽  
Vol 39 (4) ◽  
pp. 485-493 ◽  
Author(s):  
Valentina Viola ◽  
Silvia Ciffolilli ◽  
Silvia Legnaioli ◽  
Marta Piroddi ◽  
Michele Betti ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Breast Adenocarcinoma ◽  
Adenocarcinoma Cells ◽  
Her 2 ◽  
Synthetic Derivatives

scholarly journals Design, Synthesis and Anti-Platelet Aggregation Activity Study of Ginkgolide-1,2,3-triazole Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2156 ◽  
Author(s):  
Jian Cui ◽  
Le’An Hu ◽  
Wei Shi ◽  
Guozhen Cui ◽  
Xumu Zhang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Functional Groups ◽  
Ginkgo Biloba ◽  
Active Component ◽  
Platelet Activating Factor ◽  
Cycloaddition Reaction ◽  
Design Synthesis ◽  
Antiplatelet Aggregation ◽  
Ic50 Values ◽  
Aggregation Activity

Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.

scholarly journals Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4014 ◽  
Author(s):  
Dorota G. Piotrowska ◽  
Iwona E. Głowacka ◽  
Dominique Schols ◽  
Robert Snoeck ◽  
Graciela Andrei ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cytotoxic Activity ◽  
Methyl Acrylate ◽  
Rna Viruses ◽  
Dipolar Cycloaddition ◽  
Dna And Rna ◽  
Cancerous Cell ◽  
Adenocarcinoma Cells ◽  
Ic50 Values ◽  
Hct 116

Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC50 values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).

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