scholarly journals Exploring Cytotoxic Potential of Ciclopirox on Colorectal Cancer Cells by In-Silico Methodology

2021 ◽  
Vol 12 (6) ◽  
pp. 7287-7310
Keyword(s):  
Colorectal Cancer ◽  
In Silico ◽  
Drug Targets ◽  
High Mobility ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Pharmacokinetic Studies ◽  
Standard Drug ◽  
Bioisosteric Replacement ◽  
In Silico Studies

Colorectal cancer (CRC) stands 3rd among male cancer cases and the second most prevalent disease in women, accounting for 10% of all cancer cases globally. Ciclopirox (CPX) is a broad-spectrum, synthetic, off-patent antifungal drug recommended in dermatological conditions of mycoses of the skin and nails. There are no important molecular docking studies on inhibitory aspects of CPX against CRC targets. The main objective of this study was to explore the potential of CPX as an anti-CRC agent by using in-silico approaches with the help of published literature on downregulation of overhead protein expression in CRC and combining this information in order to recognize novel drug targets [Cell division cycle 25A (Cdc25A), Protein deglycase DJ-1 (DJ-1), Retinoblastoma protein (p-Rb/Rb), Cyclin-dependent kinase-4 (CDK4), High-mobility group AT-hook-2 (HMGA2), and Catenin β-1 (Wnt/-catenin)] and to identify the perspectives for drug repurposing and comparing this with oxaliplatin; one of the standard drug used in CRC. Also, in silico drug-likeliness studies, bioavailability studies, pharmacokinetic studies, drug target prediction, and bioisosteric replacement have been performed for CPX using online SwissADME tools (SwissADME, SwissTargetPrediction, and SwissBioisostere). The in silico studies revealed that CPX successfully inhibited all the molecular targets, which suggested plausible re-utilization of CPX for treating CRC.

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

Synthesis and In-silico Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Jyoti Dandriyal ◽  
Kamalpreet Kaur ◽  
Vikas Jaitak
Keyword(s):  
Anticancer Agents ◽  
Active Site ◽  
In Silico ◽  
Oral Absorption ◽  
In Vivo Studies ◽  
Conventional Heating ◽  
Microwave Assisted Synthesis ◽  
Standard Drug ◽  
In Silico Studies ◽  
Adme Properties

Background: Coumarin is a fused ring system and possesses enormous capability of targeting various receptors participating in cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of group present and its pattern of substitution on the basic nucleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ERα for anticancer activity for Breast Cancer. Method: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to -8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydrophobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heating. In-silico studies revealed that all the compounds befit in the active site of protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In future, there is a possibility of in-vitro and in-vivo studies of the synthesized compounds.

scholarly journals Synthesis, in silico studies and antibacterial activity of some novel 2-substituted benzimidazole derivatives

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Ramakrishna Chintakunta ◽  
Geethavani Meka
Keyword(s):  
Antibacterial Activity ◽  
Melting Point ◽  
In Silico ◽  
Software Tool ◽  
Benzimidazole Derivatives ◽  
Recrystallization Process ◽  
Standard Drug ◽  
In Silico Studies ◽  
Drug Synthesis ◽  
Percentage Absorption

Abstract Background The o-phenylenediamine is a versatile starting material for several compounds. Synthesized o-phenylenediamine and amino acids (glycine, alanine, aspartic acid, and l-proline) undergo condensation via Phillips reaction. The synthesized compound showed the promising antibacterial activity of Bacillus subtilis and Pseudomonas aeruginosa at the concentration of 100, 50, 25, 12.5, 6.25, 3.12, 1.6, 0.8, 0.4, and 0.2 μg/ml. Ciprofloxacin was used as standard drug. Synthesis of benzimidazole derivatives was carried out and purified by recrystallization process using ethanol. Substituted derivatives were characterized by melting point, TLC and spectroscopic methods include FT-IR and 1H-NMR. Results In silico studies were adopted for synthetic derivatives by Molinspiration, ChemDraw, and online software tool. Minimum inhibitory concentration (MIC) values of B. subtilis and P. aeruginosa were reported, and benzimidazole ligands and Molinspiration scores were generated and listed. Conclusion The more negative values indicate a higher binding affinity. The generated ligand observations can be visualized. Physical constants of synthesized derivates such as solubility and melting point were determined. Bioactivity scores were noted for different derivatives and predicted percentage absorption in the gut. The antibacterial activity was performed using the MIC method (aerobic).

scholarly journals IN SILICO STUDIES ON FUNCTIONALIZED AZAGLYCINE DERIVATIVES CONTAINING 2, 4-THIAZOLIDINEDIONE SCAFFOLD ON MULTIPLE TARGETS

2017 ◽  
Vol 9 (8) ◽  
pp. 209 ◽  
Author(s):  
Arifa Begum ◽  
Shaheen Begum ◽  
Prasad Kvsrg ◽  
Bharathi K.
Keyword(s):  
Molecular Docking ◽  
Oral Bioavailability ◽  
In Silico ◽  
Viral Infections ◽  
Target Prediction ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Molecular Docking Studies ◽  
In Silico Studies ◽  
Glycine Derivative

Objective: The 2, 4-thiazolidinedione containing compounds could lead to most promising scaffolds with higher efficiency toward the targets recognized for its antidiabetic activity when combined with azaglycine moiety. The objective of the present work was to merge functionalized aza glycines with 2, 4-thiazolidinediones, perform in silico evaluation by molecular properties prediction and undertake the molecular docking studies with targets relevant to diabetes, bacterial and viral infections using Swiss Dock programme for unraveling the target identification which can be used for further designing.Methods: (i) In silico studies were performed using Molinspiration online tool, Swiss ADME website and Swiss Target Prediction websites to compute the physicochemical descriptors, oral bioavailability and brain penetration. (ii) Molecular docking studies were performed using Swiss Dock web service for enumeration of binding affinities and assess their biological potentiality.Results: The results predicted good drug likeness, solubility, permeability and oral bioavailability for the compounds. All the compounds showed good docking scores as compared to the reference drugs. The N-oleoyl functionalized aza glycine derivative demonstrated superior binding properties towards all the studied target reference proteins, suggesting its significance in pharmacological actions.Conclusion: The binding interactions observed in the molecular docking studies suggest good binding affinity of the oleoyl functionalized aza glycine derivative, indicating that this derivative would be a promising lead for further investigations of anti-viral, anti-inflammatory and anti-diabetic activities.

In silico studies of bacterial derived fatty acid as a potential inhibitor of 1FGE and 1BQO

2021 ◽  
Vol 16 (12) ◽  
pp. 119-124
Author(s):  
S. Syed Chandini ◽  
Sairam Mantri
Keyword(s):  
Ligand Binding ◽  
Stearic Acid ◽  
In Silico ◽  
In Vivo Studies ◽  
Binding Interaction ◽  
Standard Drug ◽  
Synthetic Drugs ◽  
Potential Inhibitor ◽  
In Silico Studies

Thrombomodulin (TM) and matrix metalloproteinase (MMPs) are the major factors that are responsible for lung cancer. Hence, the identification of novel compounds inhibiting TM and MMPs is the challenging task for the scientists. Even though synthetic drugs were developed, their toxicity and offtarget limit their usage. The current study aims to investigate the molecular simulations for bacterial derived stearic acid to estimate the in silico anticancer activity against TM and MMPs protein as target compounds and the findings were correlated with the standard drug vorinostat. Using Lamarckian genetic algorithm, the TM and MMPs were energy minimized and docked with stearic acid and vorinostat using auto dock 4.2 and visualized in PyMol software. Protein and ligand binding analysis revealed that stearic acid interacts with the amino acids of MMPs residues of PHE83, SER212, ALA213 and ASN214. It interacts with the TMs with two amino acid residues i.e. CYS407 and GLU408. Hence, compared to vorinostat, stearic acid shows a higher binding affinity towards MMPs and slightly lower affinity towards TM proteinase. We conclude that the computational analysis of ligand binding interaction of stearic acid suggests that it could be a potential inhibitor of matrix metallo proteinase and is effective against thrombomodulin and can be considered as an anticancer agent by in vivo studies.

scholarly journals In Silico Studies on Fungal Metabolite against Skin Cancer Protein (4,5-Diarylisoxazole HSP90 Chaperone)

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Saravanakumar Kandasamy ◽  
Sunil Kumar Sahu ◽  
Kathiresan Kandasamy
Keyword(s):  
Methyl Ester ◽  
Skin Cancer ◽  
Secondary Metabolites ◽  
In Silico ◽  
Octadecenoic Acid ◽  
Mangrove Sediment ◽  
Heptadecanoic Acid ◽  
Standard Drug ◽  
Methyl Methyl ◽  
In Silico Studies

This work was to find out the dominant secondary metabolites derived from the fungus Trichoderma and to test them against skin cancer protein. The metabolites were extracted in 80% methanol from the fungal biomass of Trichoderma isolated from mangrove sediment. The crude methanol extract was purified and analysed for the secondary metabolites by GC-MS. Three predominant compounds (heptadecanoic acid, 16 methyl-, methyl ester; 9,12-octadecadienoic acid; cis-9-octadecenoic acid) identified in the extracts were screened against the skin cancer protein (Hsp90) by in-silico docking method. Of the compounds, heptadecanoic acid, 16 methyl, methyl ester was the most potent having the docking score of  Kcal/mol. This value was better than the standard drug “dyclonine”. This work recommends the heptadecanoic acid, 16 methyl, methyl ester for further in vitro and in vivo studies towards its development as anticancer drug.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

In Silico Studies towards Enhancing the Anticancer Activity of Phytochemical Phloretin Against Cancer Drug Targets

2018 ◽  
Vol 13 (2) ◽  
pp. 174-188 ◽  
Author(s):  
Arokia Vijaya Anand Mariadoss ◽  
Anantha Krishnan Dhanabalan ◽  
Hemalatha Munusamy ◽  
Krishnasamy Gunasekaran ◽  
Ernest David
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Drug Targets ◽  
Cancer Drug ◽  
In Silico Studies

Monosubstituted Coumarins Inhibit Epinephrine-Induced Platelet Aggregation Antiplatelet Effect of Monosubstituted Coumarins

2021 ◽  
Vol 19 ◽  
Author(s):  
Fausto Alejandro Jiménez-Orozco ◽  
Sergio Galicia-Zapatero ◽  
Edgar López-López ◽  
José L. Medina-Franco ◽  
Fernando León Cedeño ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Drug Targets ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Human Platelets ◽  
In Silico Studies ◽  
Vitro Effect ◽  
Induced Aggregation

Aim: Evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various pro-aggregatory agonists, particularly by epinephrine. Background: The emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited. Objective: Establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Using in silico studies, suggest potential drug targets to which the molecules bind to produce antiplatelet effects. Methods: The platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 µM), collagen (2 µg / ml) or ADP (10 µM). The aggregation of controls platelets was considered 100% of the response for each pro-aggregatory agonists. Results: Eleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer. Conclusions : In silico studies suggest that most active molecules might have antagonistic interactions in the adrenoceptors α2 and β2. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

scholarly journals Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4342
Author(s):  
Begüm Nurpelin Sağlık ◽  
Osman Cebeci ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
In Silico ◽  
Drug Targets ◽  
Binding Property ◽  
Spectroscopic Techniques ◽  
Design Synthesis ◽  
Piperazine Derivatives ◽  
In Silico Studies ◽  
Mao A

Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as 1H-NMR, 13C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds 3c, 3d and 3e displayed significant MAO-A inhibition potencies. Among them, compound 3e was found to be the most effective derivative with an IC50 value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC50 = 6.061 ± 0.262 µM) and clorgiline (IC50 = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound 3e and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.

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