3D QSAR studies based in silico screening of 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine analogs for anti-inflammatory activity

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

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Synthesis and Prognosis of Anti-inflammatory Activity of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3h)-one

Bulletin of Science and Practice ◽

10.33619/2414-2948/73/02 ◽

2021 ◽

Vol 7 (12) ◽

pp. 25-33

Author(s):

A. Chiriapkin ◽

I. Kodonidi ◽

A. Ivchenko ◽

L. Smirnova

Keyword(s):

Acetic Acid ◽

Biological Activity ◽

Dimethyl Sulfoxide ◽

In Silico ◽

Glacial Acetic Acid ◽

Inflammatory Activity ◽

Modified Method ◽

Anti Inflammatory ◽

Catalytic Addition ◽

Derivatives Of

The article presents a modified method for the synthesis of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one and the predict of their anti-inflammatory activity. The proposed method for obtaining tetrahydrothienopyrimidine derivatives is preparatively effective and simple. Their synthesis was carried out by heterocyclization of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in the medium of glacial acetic acid with the catalytic addition of dimethyl sulfoxide. Preliminary prognosis of anti-inflammatory activity in silico method allowed us to identify the most promising compounds. Of these, the 4b structure containing a 2-hydroxyphenyl fragment in the second position of pyrimidine-4(3H)-one may be of the greatest interest. It seems appropriate to further study the spectrum of biological activity of the studied compounds.

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In silico drug design: development of new pyrimidine-based benzo-thiazole derivatives, selective for CDK2

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210421134819 ◽

2021 ◽

Vol 18 ◽

Author(s):

Rania Kasmi ◽

Larbi Elmchichi ◽

Abdellah El Aissouq ◽

Mohammed Bouachrine ◽

Abdelkrim Ouammou

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

In Silico ◽

3D Qsar ◽

Bioactive Molecules ◽

Cancer Drugs ◽

Qsar Studies ◽

Benzothiazole Derivatives ◽

Docking Approach ◽

Potential Inhibitors

Backgroud: Kinases are proteins that control many biological functions. They are involved in cellular regulation, and many of them are deregulated in cancer proliferation. The evidence of this deregulation in many pathologies served as the origin of kinases as a therapeutic class and constitutes the motive that leads numerous teams to search for inhibitors of these targets. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Method: To design new bioactive molecules and study their interactions with the cyclin-depend kinase type 2 (CDK2) enzyme, we used two virtual screening methods: 3D-QSAR modeling and molecular docking on a series of 28 pyrimidine-based benzothiazole derivatives. Results: To develop models (3D QSAR) we used CoMFA and CoMSIA techniques using SYBYL-X2.0 molecular modeling software. The statistical parameters reveal that the good CoMFA model displays (Q²= 0.587; R²= 0.895) and that of CoMSIA displays (Q²= 0.552; R²= 0.768) which are considered to be very good internal prediction values, while an external validation of a test series of 5 compounds not included in the model development series gives R²test values of 0.56 for CoMFA and R²test values of 0.51 for CoMSIA. The molecular docking approach with AutoDockTools-1.5.6 is introduced in this work to enrich the interpretations extracted from the CoMFA and CoMSIA contour maps, and to provide an in silico research method for the most favorable mode of interaction of an inhibitor within its receptor (CDK2). Conclusion: We have constructed and validated a quantitative 3D model of structure-activity relation-ships of pyrimidine-based benzothiazole derivatives as CDK2 inhibitors. This model allows us to identify the nature and position of the groups that enhance the activity, giving us directions to discover new, more powerful molecules in a limited time.

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In silico screening of anti-inflammatory compounds from Lichen by targeting cyclooxygenase-2

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1664328 ◽

2019 ◽

Vol 38 (12) ◽

pp. 3544-3562 ◽

Cited By ~ 5

Author(s):

Tanuja Joshi ◽

Priyanka Sharma ◽

Tushar Joshi ◽

Subhash Chandra

Keyword(s):

In Silico ◽

Cyclooxygenase 2 ◽

In Silico Screening ◽

Anti Inflammatory

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In silico screening for identification of novel β-1,3-glucan synthase inhibitors using pharmacophore and 3D-QSAR methodologies

SpringerPlus ◽

10.1186/s40064-016-2589-3 ◽

2016 ◽

Vol 5 (1) ◽

Cited By ~ 6

Author(s):

Potshangbam Angamba Meetei ◽

R. .S. Rathore ◽

N. Prakash Prabhu ◽

Vaibhav Vindal

Keyword(s):

In Silico ◽

3D Qsar ◽

In Silico Screening ◽

Glucan Synthase

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Docking, 3D-QSAR studies and in silico ADME prediction on c-Src tyrosine kinase inhibitors

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2008.07.002 ◽

2009 ◽

Vol 44 (3) ◽

pp. 990-1000 ◽

Cited By ~ 36

Author(s):

Cristina Tintori ◽

Matteo Magnani ◽

Silvia Schenone ◽

Maurizio Botta

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

In Silico ◽

Kinase Inhibitors ◽

3D Qsar ◽

Src Tyrosine Kinase ◽

Qsar Studies ◽

Adme Prediction ◽

In Silico Adme Prediction

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Biological Evaluation and Docking Analysis of Daturaolone as Potential Cyclooxygenase Inhibitor

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/4098686 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Abdur Rauf ◽

Francesco Maione ◽

Ghias Uddin ◽

Muslim Raza ◽

Bina S. Siddiqui ◽

...

Keyword(s):

In Silico ◽

Biological Evaluation ◽

Inflammatory Activity ◽

Active Constituent ◽

Ligand Complex ◽

Reference Drug ◽

Paw Oedema ◽

Anti Inflammatory ◽

Dose Dependent

This study deals with the isolation of the active constituent(s) from a methanolic extract ofPistacia integerrimaJ. L. Stewart barks and it was also oriented to evaluate thein vivoandin silicoanti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound1). This compound showedin vivoa significant and dose dependent (1–30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50= 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50= 13.8 mg/kg). In thein vivoexperiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1–30 mg/kg). Moreover,in silicoanalysis of receptor ligand complex shows that compound1interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound1isolated fromP.integerrimapossessesin vivoanti-inflammatory and antinociceptive potentials, which are supportedin silicoby an interaction with COXs receptors.

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