IN-SILICO STUDIES OF ANTI-PROLIFERATIVE CURCUMIN ANALOGS

2021 ◽  
pp. 24-26
Author(s):  
Monu Kumar Shukla
Keyword(s):  
In Silico ◽  
3D Qsar ◽  
Qsar Model ◽  
Physicochemical Characteristics ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Qsar Studies ◽  
Anticancer Properties ◽  
Curcumin Analogues ◽  
In Silico Studies

Prostate cancer affects males more than women. Curcumin, a bioactive component of turmeric, reported to have anticancer properties on several cancer cell lines. Researchers utilised molecular docking to generate new curcumin analogues, quantify their characteristics, and anticipate its mode of action. In this research article QSAR studies were performed on 40 curcumin analogues using V-life MDS 3.5 software. The physicochemical characteristics were computed using Molinspiration Cheminformatics software. The best QSAR model for 2D and 3D QSAR was selected. Then ten compounds were designed and improved based on model results directly linked to activity. The in-silico approach predicted the good biological activity of compounds. Docking studies were performed using Akt1 as a probable target. Among the developed compounds, MKS50 has the best docking score (-7.175 kcal/mol). This study will provide a new path for the design, synthesis, and biological evaluation of novel curcumin analogues.

scholarly journals In silico studies on smoothened human receptor and its antagonists in search of anticancer effects

2020 ◽  
Vol 85 (3) ◽  
pp. 335-346
Author(s):  
Ana Borota ◽  
Sorin Avram ◽  
Ramona Curpan ◽  
Alina Bora ◽  
Daniela Varga ◽  
...  
Keyword(s):  
Acquired Resistance ◽  
Area Under The Curve ◽  
Weighted Average ◽  
3D Qsar ◽  
Qsar Model ◽  
Docking Studies ◽  
Receptor Inhibition ◽  
In Silico Studies ◽  
Qsar Models ◽  
Pharmacophore Hypothesis

Lately, the cancers related with abnormal hedgehog (Hh) signalling pathway are targeted by smoothened (SMO) receptor inhibitors that are rapidly developing. Still, the problems of known inhibitors such as severe side effects, weak potency against solid tumors or even the acquired resistance need to be overcome by developing new suitable inhibitors. To explore the structural requirements of antagonists needed for SMO receptor inhibition, pharmacophore mapping, 3D-QSAR models, database screening and docking studies were performed. The best selected pharmacophore hypothesis based on which statistically significant atom-based 3D-QSAR model was developed (R2 = = 0.856, Q2 = 0.611 and Pearson-R = 0.817), was further subjected to dataset screening in order to evaluate its ability to prioritize active compounds over decoys. The efficiency of one four-points pharmacophore hypothesis (AAHR.524) was observed based on good evaluation metrics such as the area under the curve (0.795), and weighted average precision (0.835), suggesting that the model is trustworthy in predicting novel inhibitors against SMO receptor.

3D QSAR Based Virtual Screening of Pyrido[1,2-a] Benzimidazoles as Potent Antimalarial Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 301-312
Author(s):  
Kalicharan Sharma ◽  
Apeksha Srivastava ◽  
Pooja Tiwari ◽  
Shweta Sharma ◽  
Mohammad Shaquiquzzaman ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antimalarial Activity ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Qsar Model ◽  
Docking Studies ◽  
Activity Data ◽  
Qsar Studies ◽  
Antimalarial Agents ◽  
Fisher Ratio

Background: Development of novel antimalarial agents has been one of the sought areas in medicinal chemistry. In this study the same was done by virtual screening of in-house database on developed QSAR model. </P><P> Methods: A six point pharmacophore model was generated (AADHRR.56) from 41 compounds using PHASE module of Schrodinger software and used for pharmacophore based search. Docking studies of the obtained hits were performed using GLIDE. Most promising hit was synthesized & biologically evaluated for antimalarial activity. </P><P> Result: The best generated model was found to be statistically significant as it had a high correlation coefficient r2= 0.989 and q2 =0.76 at 3 component PLS factor. The significance of hypothesis was also confirmed by high Fisher ratio (F = 675.1) and RMSE of 0.2745. The model developed had good predicted coefficient (Pearson R = 0.8826). The virtual screening on this model resulted in six hits, which were docked against FP-2 enzyme. The synthesized compound displayed IC50 value of 0.27&#181;g/ml against CQS (3D7) and 0.57μg/ml against CQR (RKL9). </P><P> Conclusion: 3D QSAR studies reviled that hydrophobic groups are important for anti-malarial activity while H-donor is less desirable for the same. Electron withdrawing groups at R1 position favours the activity. The biological activity data of the synthesized hit proved that the pharmacophore hypothesis developed could be utilized for developing novel anti-malarial drugs.

scholarly journals Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH2-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors

2021 ◽  
Vol 14 (4) ◽  
pp. 371
Author(s):  
Jiqing Ye ◽  
Lin Lin ◽  
Jinyi Xu ◽  
Paul Kay-sheung Chan ◽  
Xiao Yang ◽  
...  
Keyword(s):  
In Silico ◽  
Oral Absorption ◽  
Binding Pocket ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Cell Permeability ◽  
Oseltamivir Carboxylate ◽  
Enzyme Active Site ◽  
Structure Information ◽  
In Silico Studies

Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.

scholarly journals Bioassay Directed Isolation, Biological Evaluation and in Silico Studies of New Isolates from Pteris cretica L.

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 231 ◽  
Author(s):  
Saleem ◽  
Mehmood ◽  
Mehar ◽  
Khan ◽  
Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Mode ◽  
Antibacterial Activities ◽  
Chloroform Extract ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Biologically Active ◽  
Pteris Cretica ◽  
In Silico Studies ◽  
Dynamics Simulations

Members of genus Pteris have their established role in the traditional herbal medicine system. In the pursuit to identify its biologically active constituents, the specie Pteris cretica L. (P. cretica) was selected for the bioassay-guided isolation. Two new maleates (F9 and CB18) were identified from the chloroform extract and the structures of the isolates were elucidated through their spectroscopic data. The putative targets, that potentially interact with both of these isolates, were identified through reverse docking by using in silico tools PharmMapper and ReverseScreen3D. On the basis of reverse docking results, both isolates were screened for their antioxidant, acetylcholinesterase (AChE) inhibition, α-glucosidase (GluE) inhibition and antibacterial activities. Both isolates depicted moderate potential for the selected activities. Furthermore, docking studies of both isolates were also studied to investigate the binding mode with respective targets followed by molecular dynamics simulations and binding free energies. Thereby, the current study embodies the poly-pharmacological potential of P. cretica.

Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and in silico Studies

2021 ◽  
Vol 27 ◽  
Author(s):  
Bharti Rajesh Kumar Shyamlal ◽  
Manas Mathur ◽  
Dharmendra K. Yadav ◽  
Irina V. Mashevskaya ◽  
Mohamed El-Shazly ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Antiplatelet Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
In Silico Studies

Background: Several natural/synthetic molecules having structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of molecular framework, have been explored for their antioxidant or antiplatelet activities. Introduction: Based on literature, a new prototype i.e., 3-phenyl-1H-isochromen-1-ones based compounds have been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues and performing in vitro antioxidant as well as AA-induced antiplatelet activities and then, identification of potent compounds by SAR and molecular docking studies. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-folds to 16-folds highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost, all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship and in silico studies of pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

Discovery of novel cinnamylidene-thiazolidinedione derivatives as PTP-1B inhibitors for the management of type 2 diabetes

RSC Advances ◽  
2016 ◽  
Vol 6 (110) ◽  
pp. 108928-108940 ◽  
Author(s):  
Suresh Thareja ◽  
Sant K. Verma ◽  
Diksha Haksar ◽  
Tilak R. Bhardwaj ◽  
Manoj Kumar
Keyword(s):  
Type 2 Diabetes ◽  
Binding Affinity ◽  
In Silico ◽  
3D Qsar ◽  
Biological Evaluation ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Qsar Studies ◽  
Ptp 1B

Synthesis, biological evaluation,in silicobinding affinity prediction and 3D-QSAR studies of cinnamylidene-thiazolidinedione derivatives was performed as inhibitors of PTP-1B.

Non-Nucleoside HIV-1 Reverse Transcriptase Inhibition Activity of a Series of Dihydroalkoxybenzyloxopyrimidine (DABO) Derivatives: CoMFA, CoMSIA and Docking Studies

2020 ◽  
Vol 5 (3) ◽  
pp. 265-272
Author(s):  
Bikash Kumar Sarkar ◽  
Ananda Sarkar ◽  
Atish Dipankar Jana
Keyword(s):  
3D Qsar ◽  
Docking Study ◽  
Binding Pocket ◽  
Qsar Model ◽  
Docking Studies ◽  
Field Analysis ◽  
Qsar Studies ◽  
3D Space ◽  
Pyrimidine Moiety ◽  
Hiv 1

CoMFA, CoMSIA and molecular docking studies have been carried out for a set of 42 dihydroalkoxybenzyloxopyrimidine (DABO) derivatives for which anti-HIV activity values are available. In 3D-QSAR studies-comparative molecular field analysis (CoMFA) as well as comparative molecular similarity indices analysis (CoMSIA) have been performed. Both the QSAR model nicely explains the inhibitory activities of DABO derivatives as well as provides molecular level insights revealing which regions in 3D space around the molecules are more important for their anti HIVactivities. These models have a quite high square correlation coefficient (r2 = 0.817 for CoMFA and r2 = 0.943 for CoMSIA). A docking study of the highest active molecule into the binding site of the protein HIV-1 RT (PDB ID-1RT1) shows that hydrogen bonding between pyrimidine moiety of the ligand and the Lysine-101 moiety along with Valine-106 moiety of the HIV protein play most important role for stabilizing the ligand in the binding pocket of the protein.

scholarly journals Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors

2014 ◽  
Vol 15 (5) ◽  
pp. 8795-8807 ◽  
Author(s):  
Hui Wang ◽  
Zhiyun Du ◽  
Changyuan Zhang ◽  
Zhikai Tang ◽  
Yan He ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
3D Qsar ◽  
Biological Evaluation ◽  
Qsar Studies ◽  
Curcumin Analogues ◽  
Aldehyde Dehydrogenase 1

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Enzymatic Textile Dyes Decolorization by In vitro and In silico Studies

2019 ◽  
Vol 13 (4) ◽  
pp. 268-276
Author(s):  
Sridevi Ayla ◽  
Monika Kallubai ◽  
Suvarnalatha Devi Pallipati ◽  
Golla Narasimha
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Textile Dyes ◽  
Crude Enzyme ◽  
Eastern Ghats ◽  
Textile Dye ◽  
Phanerochaete Sordida ◽  
Molecular Docking Studies ◽  
In Silico Studies

Background:Laccase, a multicopper oxidoreductase (EC: 1.10.3.2), is a widely used enzyme in bioremediation of textile dye effluents. Fungal Laccase is preferably used as a remediating agent in the treatment and transformation of toxic organic pollutants. In this study, crude laccase from a basidiomycetes fungus, Phanerochaete sordida, was able to decolorize azo, antroquinone and indigoid dyes. In addition, interactions between dyes and enzyme were analysed using molecular docking studies.Methods:In this work, a white rot basidiomycete’s fungus, Phanerochaete sordida, was selected from forest soil isolates of Eastern Ghats, and Tirumala and lignolytic enzymes production was assayed after 7 days of incubation. The crude enzyme was checked for decolourisation of various synthetic textile dyes (Vat Brown, Acid Blue, Indigo, Reactive Blue and Reactive Black). Molecular docking studies were done using Autodock-4.2 to understand the interactions between dyes and enzymes.Results:Highest decolourisation efficiency was achieved with the crude enzyme in case of vat brown whereas the lowest decolourisation efficiency was achieved in Reactive blue decolourisation. Similar results were observed in their binding affinity with lignin peroxidase of Phanerochaete chrysosporium through molecular docking approach.Conclusion:Thus, experimental results and subsequent in silico validation involving an advanced remediation approach would be useful to reduce time and cost in other similar experiments.

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