scholarly journals Ethanolic Extract of Hedyotis corymbosa and Its Combination with 5-FU Inhibit Cyclin D Expression on WiDr Colorectal Cancer Cell

2017 ◽  
Vol 7 (1) ◽  
pp. 25 ◽  
Author(s):  
Argandita Meiftasari ◽  
Januar Caesar W.P. ◽  
Annisa Novarina ◽  
Julika Yovi W. ◽  
Riris Istighfari Jenie
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Ursolic Acid ◽  
Cancer Cell ◽  
Docking Simulation ◽  
Ethanolic Extract ◽  
Docking Study ◽  
Antiproliferative Effect ◽  
Cyclin D ◽  
Molecular Docking Study

Hedyotis corymbosa has been used for long time as an important component in several folklore medicine formula to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, Hedyotis corymbosa ethanolic extract (HEE) which contain ursolic acid reported to inhibit CRC growth via induction of cancer cell apop­tosis and blocked the cell cycle, preventing G1 to S progression where cyclin D highly espressed in this phase. 5-fluorouracil (5FU), the first line chemotherapy of colorectal cancer have had resistence and possessed several side effects such as neutropenia, immunosuppression, diarrhea, and also constipation. Therefore, the aim of this research is to conduct the antiproliferative effect and molecular analysis of HEE and its combination with 5FU. Molecular docking study was also done to approach the specific protein target of the compound. Antiproliferative effect was conducted by MTT assay, while cyclin D expression  was examined by immunofluorescence. The proliferative effect showed that both HEE and 5-FU had cytotoxic effect with IC50 value of 65 µg/mL and 90 µM respectively, meanwhile the combination of HEE and 5FU have synergism effect with CI = 0.48 on dose HEE = 22 µg/mL and 5FU= 6.25 µM. Immunofluorescence assay showed HEE and its combination with 5FU suppressed the expression of cyclin D. From molecular docking simulation, ursolic acid performed stable interaction with cyclin D. Our findings suggest that HEE may be an effective treat­ment for co-chemotherapic for 5-FU through inhibition of cyclin D expression.Keywords : Hedyotis corymbosa, 5-fluorouracil, colorectal cancer,  WiDr, cyclin D 

Molecular docking study of Keji Beling leave compound as protein 1J4X inhibitor to cervical cancer cell

2021 ◽  
Author(s):  
Rita Arbianti ◽  
Fauzul Fadli ◽  
Tania Surya Utami ◽  
Yuswan Muharam ◽  
Slamet
Keyword(s):  
Cervical Cancer ◽  
Molecular Docking ◽  
Cancer Cell ◽  
Docking Study ◽  
Cervical Cancer Cell ◽  
Molecular Docking Study

scholarly journals Iron Chelation Properties of Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zarith Nameyrra Md Nesran ◽  
Nurul Husna Shafie ◽  
Siti Farah Md Tohid ◽  
Mohd Esa Norhaizan ◽  
Amin Ismail
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Green Tea ◽  
Iron Chelation ◽  
Docking Study ◽  
Therapeutic Effects ◽  
Molecular Docking Study ◽  
Colorectal Cancer Cells

In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (−7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71; two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.

scholarly journals In silico design and molecular docking study of CDK2 inhibitors with potent cytotoxic activity against HCT116 colorectal cancer cell line

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Fabian Adakole Ikwu ◽  
Yusuf Isyaku ◽  
Babatunde Samuel Obadawo ◽  
Hadiza Abdulrahman Lawal ◽  
Samuel Akolade Ajibowu
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Side Effects ◽  
In Silico ◽  
Molecular Descriptors ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Qsar Model ◽  
Colorectal Cancer Cell Line ◽  
Molecular Docking Study

Abstract Background Colorectal cancer is common to both sexes; third in terms of morbidity and second in terms of mortality, accounting for 10% and 9.2% of cancer cases in men and women globally. Although drugs such as bevacizumab, Camptosar, and cetuximab are being used to manage colorectal cancer, the efficacy of the drugs has been reported to vary from patient to patient. These drugs have also been reported to have varying degrees of side effects; thus, the need for novel drug therapies with better efficacy and lesser side effects. In silico drugs design methods provide a faster and cost-effect method for lead identification and optimization. The aim of this study, therefore, was to design novel imidazol-5-ones via in silico design methods. Results A QSAR model was built using the genetic function algorithm method to model the cytotoxicity of the compounds against the HCT116 colorectal cancer cell line. The built model had statistical parameters; R2 = 0.7397, R2adj = 0.6712, Q2cv = 0.5547, and R2ext. = 0.7202 and revealed the cytotoxic activity of the compounds to be dependent on the molecular descriptors nS, GATS5s, VR1_Dze, ETA_dBetaP, and L3i. These molecular descriptors were poorly correlated (VIF < 4.0) and made unique contributions to the built model. The model was used to design a novel set of derivatives via the ligand-based drug design approach. Compounds e, h, j, and l showed significantly better cytotoxicity (IC50 < 5.0 μM) compared to the template. The interaction of the compounds with the CDK2 enzyme (PDB ID: 6GUE) was investigated via molecular docking study. The compounds were potent inhibitors of the enzyme having binding affinity of range −10.8 to −11.0 kcal/mol and primarily formed hydrogen bond interaction with lysine, aspartic acid, leucine, and histidine amino acid residues of the enzyme. Conclusion The QSAR model built was stable, robust, and had a good predicting ability. Thus, predictions made by the model were reliably employed in further in silico studies. The compounds designed were more active than the template and showed better inhibition of the CDK2 enzyme compared to the standard drugs sorafenib and kenpaullone.

scholarly journals New 1,2,3-Triazole-Containing Hybrids as Antitumor Candidates: Design, Click Reaction Synthesis, DFT Calculations, and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 708
Author(s):  
Islam H. El Azab ◽  
Hamdy S. El-Sheshtawy ◽  
Rania B. Bakr ◽  
Nadia A. A. Elkanzi
Keyword(s):  
Molecular Docking ◽  
Dft Calculations ◽  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Hct 116 ◽  
Mcf 7

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were in vitro estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC50 = 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies 7, 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

scholarly journals SYNTHESIS, MOLECULAR DOCKING AND ANTI-PROLIFERATIVE ACTIVITY OF NEW SERIES OF 1-METHYLSULPHONYL-3-INDOLYL HETEROCYCLES

2016 ◽  
Vol 8 (12) ◽  
pp. 113 ◽  
Author(s):  
Heba M. Abo-salem ◽  
Khadiga M. Ahmed ◽  
Salwa El- Hallouty ◽  
Eslam R. El-sawy ◽  
Adel H. Mandour
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Cell Line ◽  
Cancer Cell ◽  
Active Site ◽  
Proliferative Activity ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ca Ix

<p><strong>Objective</strong>:<strong> </strong>The present work aimed to synthesize a new series of 1-methylsulphonyl-3-indolyl heterocycles and study their cytotoxic activity. In addition, we attempted to explore the mode of the interaction of anti-proliferative compounds with the active site of carbonic anhydrase IX (CA IX) theoretically <em>via</em> molecular docking study.</p><p><strong>Methods</strong>:<strong> </strong>Novel series of pyrazole, pyrimidine and triazole derivatives bearing 1-methylsulphonyl-1<em>H</em>-indole were prepared <em>via</em> a series of hetero cyclization reactions utilizing 3-(1-methylsulphonyl-1<em>H</em>-indol-3-yl)-1-(substituted phenyl)-1<em>H</em>-pyrazole-4-carboxaldehydes 3a-d and 3-chloro-3-(1-methylsulphonyl-1<em>H</em>-indol-3-yl)propenal (6) and evaluating their anti-proliferative activity. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, NMR and mass spectral data. In addition, molecular docking study of the most promising antiproliferative compounds against the active site of carbonic anhydrase IX (PDB ID: 4BCW) theoretically is discussed.</p><p><strong>Results</strong>:<strong> </strong>Compounds 5c, 7 and 12 revealed potent anti-proliferative effects against A-549 cancer cell line with IC<sub>50</sub> of 44.3, 17.2 and 38.7 µmol/l, respectively compared to the reference drug doxorubicin (IC<sub>50</sub> of 48.8 µmol/l). While compound <strong>5c</strong> was found to be highly active with IC<sub>50</sub> of 5.66 µmol/l against HCT-116 cancer cell line than doxorubicin (IC<sub>50</sub> of 65.00 µmol/l).</p><p><strong>Conclusion</strong>:<strong> </strong>Further work is recommended to confirm the inhibition of CA IX in a specific bioassay.</p>

Acetogenins Exhibit Potential BCL-XL Inhibitor for the Induction of Apoptosis in the Molecular Docking Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Noraziah Nordin ◽  
Kaynat Khimani ◽  
Mohd Faiz Abd Ghani
Keyword(s):  
Molecular Docking ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Properties ◽  
Vital Role ◽  
Molecular Docking Study ◽  
Good Target ◽  
Induction Of Apoptosis

Background: Anti-apoptotic protein BCL-XL plays a vital role in tumorigenesis and cancer chemotherapy resistance, resulting in a good target for cancer treatment. Understanding the function of BCL-XL has driven the progression of a new class of cancer drugs that can mimic its natural inhibitors, BH3-only proteins to trigger apoptosis. This mimicking is initiated through acetogenins due to their excellent biological properties. Acetogenins which can be isolated from Annonaceae plants, have a unique structure along with several oxygenated functionalities. Objective: Based on their biological capability, various acetogenins were studied in the present study and compared alongside with ABT-737 on molecular docking. Methods: The docking simulation of acetogenins was performed using AutoDock Vina software. Results: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than – 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11) and isoannonacin-10-one A (18). Conclusion: These findings indicated that some acetogenins could represent a new potential BCL-XL inhibitor which could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.

scholarly journals Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ramalingam Srinivasan ◽  
Arumugam Aruna ◽  
Jong Suk Lee ◽  
Myunghee Kim ◽  
Muthugounder Subramaniam Shivakumar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Ursolic Acid ◽  
Topoisomerase Ii ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Bioactive Molecules ◽  
Molecular Docking Study ◽  
Docking Approach ◽  
Free Radicals Scavenging

The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC50 values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (−8.0312) and GLIDE energy (−51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

scholarly journals Synthesis, Antimicrobial Study, and Molecular Docking Simulation of 3,4-Dimethoxy-β-Nitrostyrene Derivatives as Candidate PTP1B Inhibitor

2020 ◽  
Vol 88 (3) ◽  
pp. 37
Author(s):  
Salman Alfarisi ◽  
Mardi Santoso ◽  
Alfinda Novi Kristanti ◽  
Imam Siswanto ◽  
Ni Nyoman Tri Puspaningsih
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Metabolic Diseases ◽  
Tyrosine Phosphatase ◽  
Docking Simulation ◽  
Docking Study ◽  
Negative Regulator ◽  
Potential Candidate ◽  
Molecular Docking Study ◽  
Cell Functions

A derivative series of 3,4-dimethoxy-β-nitrostyrene was synthesized through nitroaldol reaction, including a new compound of 3,4-ethylenedioxy-β-bromo-β-nitrostyrene. The antimicrobial activity effect of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking study was also performed to obtain information about their interactions with protein tyrosine phosphatase 1B (PTP1B). The active residues of cysteine-215 and arginine-221 of PTP1B play a key role in signaling pathways that regulate various microorganism cell functions. It also acts as a negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. These derivatives exhibited potential antifungal activity. The studied compounds were also had potential as fragments to be PTP1B inhibitors by interacting with serine-216 and arginine-221 residues, according to their molecular docking. 3,4-Ethylenedioxy-β-methyl-β-nitrostyrene was the most successful potential candidate as a PTP1B inhibitor. However, further research is needed to investigate their potential for medicinal use.

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