scholarly journals Molecular docking studies of potential anticancer agents from Thunbergia Fragrans against Colorectal cancer mutant genes through In silico study

2021 ◽  
Vol 12 (4) ◽  
pp. 792-795
Author(s):  
Charankumar Chandrasekaran ◽  
Ramar K
Keyword(s):  
Colorectal Cancer ◽  
Binding Energy ◽  
Palmitic Acid ◽  
Anticancer Activity ◽  
Chemical Constituents ◽  
Docking Studies ◽  
Flowering Plant ◽  
Beta Catenin ◽  
Effective Manner ◽  
Mutant Genes

Colorectal cancer (CRC) is one of the deadly diseases which incidence rate will increase every year due to people lifestyle and food habit etc., Moreover, people’s required a new therapeutic molecule to resolve this problem. Therefore plant-based chemical constituents are the best option due to the low side effects, easy availability and cost-effective manner. The flowering plant of Thunbergia fragrans Roxb belongs to the Acanthaceae family has a vast range of medicinal properties, anticancer activity is one among them. Thunbergia fragrans has reported to had chemical constituents of Palmitic acid, Cis-9-Hexadecenal and Campesterol which possess anticancer activity. For the beginning of TF chemical constituents were studied against the Colorectal cancer (CRC) mutant genes such as NRAS (PDB ID: 6ZIZ), Beta-Catenin (PDB ID: 6M93) – Oncogenes; APC (PDB ID: 3NMX), Smad2 (PDB ID: 1KHU) – Tumor Suppressor genes through insilico docking studies. AutoDock 4.2 tool was used to predict the interaction between ligand and receptor, Binding energy and Bond specification in a 3D space. Finally, the results revealed TF chemical constituents showed excellent binding energy against CRC mutant genes such as Palmitic acid against Beta-Catenin (-4.75) and APC (-4.01), Cis-9-Hexadecenal against NRAS (-1.92), Beta-Catenin (-3.96) and APC (-4.41), Campesterol against Beta-Catenin (-8.55) and APC (-8.85) respectively. 

scholarly journals STRUCTURE-BASED DOCKING STUDIES TOWARD EXPLORING THE POTENTIAL ANTICANCER ACTIVITY OF MORIN AGAINST NON-MELANOMA SKIN CANCER THERAPEUTIC DRUG TARGETS

2018 ◽  
Vol 11 (4) ◽  
pp. 61
Author(s):  
Anjugam C ◽  
Sridevi M ◽  
Gnanendra Ts
Keyword(s):  
Binding Energy ◽  
Anticancer Activity ◽  
Drug Targets ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Peroxisome Proliferator ◽  
Non Melanoma Skin Cancer ◽  
Cox 2 ◽  
Peroxisome Proliferator Activated Receptors ◽  
In Silico Molecular Docking

 Objective: The purpose of this study is to explore the anticancer activity of morin compound against human cyclooxygenase-2 (COX-2) and peroxisome-proliferator-activated receptors (PPARs) isotypes (PPARα and PPARγ) through in silico molecular docking studies.Methods: The 3D structures of human COX-2 complexed with ibuprofen (PDB ID: 4PH9), PPARα complexed with a synthetic agonist (2S)-2-(4- methoxy-3-{[(pyren-1-yl carbonyl) amino] methyl} benzyl) butanoic acid (PDB ID: 3VI8) and PPARγ complexed indomethacin (PDB ID: 3ADX) were retrieved from protein databank. The cocrystallized sites were considered as binding sites, and the docking with morin compound was performed along with their respective cocrystals for each target and compared their interactions and binding affinities.Results: It is observed that the morin compound exhibited better binding energy of -32.9528 kJ/mol against PPARα followed by COX-2 (binding energy: −18.4311 kJ/mol) and PPARγ (binding energy: −17.4228 kJ/mol) when compared to their cocrystallized ligands.Conclusion: The present study suggests that morin compound might serve as potential alternatives in the prevention of skin cancers by showing better activity against PPARα.

Cytotoxic Evaluation and Molecular Docking studies of Aminopyridine derivatives as Potential Anticancer Agents

2021 ◽  
Vol 22 ◽  
Author(s):  
Umair Ilyas ◽  
Shagufta Naaz ◽  
Syed Aun Muhammad ◽  
Humaira Nadeem ◽  
Reem Altaf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
In Silico ◽  
Cancer Cell Line ◽  
Docking Studies ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Line ◽  
Beta Catenin ◽  
Hct 116

Background: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure. Objectives: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2-aminopyridine could attenuate tumor development using colorectal cancer cell lines. Methods: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. Results: The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1µM and 3.27-7.7 µM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 µg/ml. Conclusion: In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.

Molecular Docking, G-QSAR Studies, Synthesis and Anticancer Screening of Some New 2-Phenazinamines as Bcr-Abl Tyrosine Kinase Inhibitors

2020 ◽  
Vol 17 (2) ◽  
pp. 213-224
Author(s):  
Mayura A. Kale ◽  
Gajanan M. Sonwane
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Tyrosine Kinase ◽  
Anticancer Activity ◽  
Cell Line ◽  
Kinase Inhibitors ◽  
Docking Studies ◽  
Abl Tyrosine Kinase ◽  
Standard Doxorubicin ◽  
Wet Lab

Background: The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. Methods: The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet lab experiments for synthesizing 2- phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimised by using semiempirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. Later, we synthesized novel 13 2-phenazinamine derivatives by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazin-2-yl) thiazolidin-4-one and another series of derivatives synthesized with different aldehydes in the presence of p-toluylsulphonic acid, diphydropyridine and benzene sulfonyl chloride to afford benzenesulfonyl-N-(2-chlorobenzyl)-phenazin-2-amine. All the derivatives were tested for invitro anticancer activity on K562 human chronic myelogenous leukemia cell line by employing MTT assay method. Results: The developed G-QSAR models were found to be statistically significant with respect to training (r2=0.8074), cross-validation (q2=0.6521), and external validation (pred_r2=0.5892). The best developed G-QSAR model suggested that the XlogP values of phenazinamine derivatives were found to be highly influential in determining biological activity. The standard drug was found to exhibit binding energy - 6.79 kcal/mol and the derivatives 5b and 6c exhibited binding energy of - 7.46 and - 8.51; respectively. Conclusion: Compounds 5b, 6c were observed to possess good lipophilicity and were found to exhibit better activity than other compounds in the series, although less than standard doxorubicin. The synthesis of these 2-phenazinamine derivatives (5a-m) is reported to be obtained from 2,4- dinitrodiphenylamine by applying appropriate synthetic route. Compounds 5b and 6c showed better cytotoxic activity against K562 cancer cell line when compared to other compounds of the series, although less than standard doxorubicin.

Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

2019 ◽  
Vol 19 (13) ◽  
pp. 1093-1110 ◽  
Author(s):  
Adel A.H. Abdel Rahman ◽  
Ibrahim F. Nassar ◽  
Amira K.F. Shaban ◽  
Dina S. EL-Kady ◽  
Hanem M. Awad ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Human Liver ◽  
Docking Studies ◽  
Cyclin Dependent Kinase ◽  
Binding Interaction ◽  
Enzyme Active Site ◽  
Human Liver Cancer ◽  
Amino Derivatives ◽  
Activity Behavior ◽  
Derivatives Of

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

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.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Structural and Molecular Docking Studies of 4-Benzyl-3-[(1-methylpyrrol- 2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with Anticancer Activity

2013 ◽  
Vol 9 (3) ◽  
pp. 313-328 ◽  
Author(s):  
Agnieszka A. Kaczor ◽  
Monika Pitucha ◽  
Zbigniew Karczmarzyk ◽  
Waldemar Wysocki ◽  
Jolanta Rzymowska ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Docking Studies ◽  
Molecular Docking Studies

Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Srinu Bodige ◽  
Parameshwar Ravula ◽  
Kali Charan Gulipalli ◽  
Srinivas Endoori ◽  
J.N. Narendra Sharath Chandra ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Intracellular Signaling ◽  
Research Work ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Intracellular Enzyme ◽  
Ht 29 ◽  
Mcf 7

Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. Methods: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme. Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM. Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.

Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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