scholarly journals An in silico evaluation of CDK Inhibitors targeting BCL2, TS and mTOR

2021 ◽  
Vol 7 (2) ◽  
pp. 126-131
Author(s):  
Sharmin Ahmed Rakhi ◽  
Muhammad Asaduzzaman ◽  
Nishat Nasin ◽  
Abul Bashar Mir Md Khademul Islam
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
In Silico ◽  
Target Therapy ◽  
Research Work ◽  
Chemotherapeutic Agents ◽  
Physical Interaction ◽  
Cdk Inhibitors ◽  
Molecular Docking Study ◽  
Human Cancers

The cyclin dependent kinase (CDK) inhibitors have recently been found to be of potential use as anticancer drugs. The present research work focuses on screening of compounds targeting multiple pathways involved in human cancers along with CDK-regulated cell cycle for prospective anticancer potential. Molecular docking study of selected compounds were performed to determine the binding affinity of selected compounds towards respective targets of cancer cells to verify if there is any physical interaction of these inhibitors with their reported target proteins as claimed in the existing literatures. Prior to docking, molecular pathway prediction and gene set enrichment analyses were performed to identify the target molecules by using appropriate bioinformatics tools. Interestingly, the results of in silico molecular docking have been found to be in line with the laboratory findings that are obtained from the literatures. Specifically, few of our selected CDK inhibitors, namely Abemaciclib, Palbociclib, AMG 925 and RGB 286638 showed good binding scores against BCL2, TS, mTOR in addition to CDKs (4, 6 and 9). On the basis of scientific evidence based on published scholarly articles and according to molecular docking results, it can be inferred that these CDK inhibitors as anticancer agents may play a very promising role in cancer treatment and can be used as potential lead compounds for the development of target therapy against human cancers. However, more intensive research is needed to confirm the feasibility of these compounds to be used in treating cancer and it is expected that this work will provide a stimulating impetus for the development of chemotherapeutic agents in future. Asian J. Med. Biol. Res. 2021, 7 (2), 126-131

scholarly journals In silico Study of the Interactions between Schiff Base Polyphenols and HPV 16 E6/E6AP/p53 complex

2021 ◽  
pp. 3973-3980
Author(s):  
Jeremiah I. Ogah ◽  
Olatunji M. Kolawole ◽  
Steven O. Oguntoye ◽  
Muhammed Mustapha Suleiman
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
In Silico ◽  
In Silico Analysis ◽  
Docking Study ◽  
Hydrogen Atoms ◽  
Molecular Docking Study ◽  
Hpv 16 ◽  
In Silico Study

The rise in the incidence of cervical cancer globally has accentuate attention to the potential role of polyphenols as anticancer agents. Different studies have demonstrated the role of some polyphenols in altering Human Papillomavirus (HPV) carcinogenesis. Thus, this study was aimed at establishing the potentials of Schiff-based polyphenols from imesatin and satin as anticancer agents through in silico analysis. The polyphenols were synthesized and characterized using elemental analyses, spectroscopic analyses, UV-visible, Infrared, and Nuclear Magnetic Resonance (1H NMR and 13C, NMR). Molecular docking study of the polyphenols was carried out using Auto Dock Vina. The oncogenic E6 protein structure of HPV 16 was obtained from the protein bank (ID: 4XR8). The E6 proteins were prepared using AutoDock tools. Water molecules were removed from the protein molecules while hydrogen atoms were added. Also, the structures of Curcumin and Isomericitrin were obtained from PubChem. Results showed that three different Schiff based polyphenols were obtained from the synthesis; 3-(2’,4’-dimethoxy benzylidene hydrazono) indoline-2-one (DMBH), 3-(2’-hydroxy-4’-methoxy benzylidene hydrazono) indoline-2-one (HMBD), and 3-((4-4’-((2’’, 4’’-dimethoxy benzylidene amino) benzyl)phenyl)imino) indoline-2-one (DMBP). Higher ability of the docked polyphenols to bind to the E6/E6AP/p53 complex when compared to Curcumin was revealed. Also, results showed that the binding energy of Curcumin and Isomericitrin were -7.1kcal/mol and -8.4kcal/mol respectively while that of the polyphenols ranged from -7.4kcal/mol to -7.9kcal/mol. The molecular docking results of the polyphenols used in this study further confirm their potentials as strong anti-cancer agents.

Design, Synthesis, and Characterization of Novel Linomide Analogues and their Evaluation for Anticancer Activity

2020 ◽  
Vol 17 (2) ◽  
pp. 203-212
Author(s):  
Rudrax N.S. Priolkar ◽  
Sunil Shingade ◽  
Mahesh Palkar ◽  
Shivalingrao M. Desai
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Research Work ◽  
Chemotherapeutic Agents ◽  
Primary Amines ◽  
Tyrosine Kinase Domain ◽  
Compound Ii

Background: According to WHO, in 2017, about 90.5 million people suffered from cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic agents have decreased the mortality among the cancer patients but high toxicity and non-specific targets are still major drawbacks. : Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for the development of anticancer agents. With this background, we thought of the following objective. Objective: The objective of this research work involves the synthesis of a series of N-(2-(4- hydroxy-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-oxoethyl)-N-alkyl substituted benzene sulfonamides IVa-d (1-3) by replacing the anilide moiety at the third position of linomide with sulfamoylacyl and also N-methyl by N-phenyl functionality. To perform in silico anticancer activity by using Molegro Virtual Docker (MVD-2013, 6.0) software and in vitro anticancer activity by MTT assay. Methods: The starting material 4-hydroxy-1-phenylquinolin-2(1H)-one was treated with N-bromosuccinamide to yield compound II. Condensation of compound II with primary amines resulted in compounds IIIa-d, which, on coupling with substituted aromatic sulfonyl chlorides yield the title compounds IVa-d (1-3). Results: All the synthesized compounds were satisfactorily characterized by spectral data. The results of docking revealed that the synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain (PDB ID: 1m17). The MolDock Score of compound IVd-1 (-115.503) was the highest amongst those tested. The in vitro anticancer activity results showed that compound IVc-1 (R= - (CH2) 2-CH3 ; R′= -H) and IV d-1 (R= -CH2-C6H5; R′= -H) were found to be most potent against K562 cell line with an IC50 of 0.451 μM/ml and 0.455 μM/ml respectively. Compound IVd-1 also showed better potency against A549 cell line with IC50 value of 0.704 μM/ml. Conclusion: The results of in silico and in vitro anticancer activity are in agreement with each other. Compound IV d-1 was found to be most active of the series.

scholarly journals In Silico studies of 4-Anilino Quinazoline derivatives as Anti-tubercular Agents

2020 ◽  
Vol 11 (4) ◽  
pp. 7468-7475
Author(s):  
Hemalatha K ◽  
Sujatha K ◽  
Panneerselvam P ◽  
Girija K
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Resistant Strain ◽  
In Silico ◽  
Research Work ◽  
Docking Study ◽  
Molecular Docking Study ◽  
In Silico Studies ◽  
Quinazoline Derivatives ◽  
Mycobacterial Cell Wall

Inh A, the Enoyl Acyl Carrier protein Reductase from Mycobacterium tuberculosis is one of the pivotal enzyme involved in the mycobacterial fatty acid elongation cycle and has been considered as an important target for anti-tubercular screening. Inhibition of Inh A affects the biosynthesis of the mycolic acids, which are the central constituents of the mycobacterial cell wall. In the present research work, 4-anilino quinazoline derivatives were designed based on the quinazoline based drugs by means of lipophilic insertion and Fragment replacement. The designed compounds were synthesized, and molecular docking studies were performed on the human pathogenic bacterial enzyme InhA from its parent domain Mycobacterium Tuberculosis. Molecular docking study revealed that compounds SMOQ2, SNAQ3, 4AAQ7, 2AP9, PABAQ10 were found to possess good binding affinity towards the target InhA. With reference to the binding energy obtained from molecular docking study, five compounds were subjected to in vitro anti-tubercular activity against M. tuberculosis  H37Rv and I2487 (Resistant strain) using BACTEC MGIT method. Compound SMOQ2 and 4AAQ7 showed sensitivity in both H37Rv (Sensitive strain) and I2487 (Resistant strain) at the concentration of 250, 500, 1000 and 1500 mcg/mL. In silico Pharmacokinetic predictions of the synthesized compounds were determined using SwissADME online web tool. All the synthesized compounds obeyed the Lipinski's rule of five properties.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

scholarly journals Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

Molecular Docking Study of Bio-Inhibitors Extracted From Marine Macro Alga Ulva Fasciata Against Hemolysin Protein of luminescence Disease Causing Vibrio Harveyi

2021 ◽  
Author(s):  
Krishnamoorthy Sivakumar ◽  
Sudalayandi Kannappan ◽  
Balakrishnan Vijayakumar ◽  
Jithendran Karingalakkandy Poochirian ◽  
Sivamani Balasubramanian ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Tamil Nadu ◽  
Pathogenic Bacteria ◽  
Vibrio Harveyi ◽  
Penaeus Monodon ◽  
Chemotherapeutic Agents ◽  
Computer Assisted ◽  
Bacterial Disease ◽  
Molecular Docking Study ◽  
Ulva Fasciata

Abstract Shrimp grow-out and hatchery systems are being affected by bacterial disease particularly Vibrios. The use of chemotherapeutic agents in aquaculture practices has to lead to the development of resistance among aquatic bacteria. Thus, health management becomes of major importance in aquaculture. Under this situation, progressing bio-inhibitors from marine resources are most appropriate to be considered against pathogenic bacteria. Molecular docking is an appropriate tool in structural biology and computer-assisted drug design to predict and neutralize a target protein of known diseases. In this study, marine macroalga Ulva fasciata was aimed at developing inhibitors against luminescence disease-causing pathogenic bacteria Vibrio harveyi. U. fasciata was collected from the intertidal zone of Thoothukudi, Tamil Nadu, India. Extract of U. fasciata was tested against growth and virulence factors of V. harveyi during Penaeus monodon larviculture. For molecular docking, the homology modeling of virulence of hemolysin protein of V. harveyi was designed and used for docking studies against the compounds of U. fasciata as identified by GC-MS analysis. Extract of U. fasciata@200 mg mL-1 had exhibited reductions on Cumulative Percentage of Mortality (32.40%) in postlarvae against the challenge of V. harveyi infection. In docking analysis, the bio-inhibitor Methyl dehydroabietate showed the highest binding affinity among compounds docked. Statistical analysis had revealed significant differences (p<0.05) in trials. Therefore, it was proved that the bio-inhibitors from U. fasciata will be a better option for controlling luminescence disease-causing V. harveyi in shrimp grow-out practices.

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