Synthetic Analogues of Aminoadamantane as Influenza Viral Inhibitors—In Vitro, In Silico and QSAR Studies

A series of nineteen amino acid analogues of amantadine (Amt) and rimantadine (Rim) were synthesized and their antiviral activity was evaluated against influenza virus A (H3N2). Among these analogues, the conjugation of rimantadine with glycine illustrated high antiviral activity combined with low cytotoxicity. Moreover, this compound presented a profoundly high stability after in vitro incubation in human plasma for 24 h. Its thermal stability was established using differential and gravimetric thermal analysis. The crystal structure of glycyl-rimantadine revealed that it crystallizes in the orthorhombic Pbca space group. The structure–activity relationship for this class of compounds was established, with CoMFA (Comparative Molecular Field Analysis) 3D-Quantitative Structure Activity Relationships (3D-QSAR) studies predicting the activities of synthetic molecules. In addition, molecular docking studies were conducted, revealing the structural requirements for the activity of the synthetic molecules.

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3D QSAR Studies on Cytotoxicity of Ent-Kauranoids against K562 Cells by CoMFA

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.554-556.1853 ◽

2012 ◽

Vol 554-556 ◽

pp. 1853-1856 ◽

Cited By ~ 1

Author(s):

Ping Yi ◽

Jin Yang ◽

Du Shu Huang

Keyword(s):

Theoretical Basis ◽

K562 Cells ◽

3D Qsar ◽

Field Analysis ◽

Comparative Molecular Field Analysis ◽

Design Work ◽

Qsar Studies ◽

Natural Drugs ◽

The Relationship

AIM: To establish the CoMFA models of the ent-kauranoids and give the theoretical basis to guide the design of the new drug. METHODS and RESULTS: The advanced 3D-QSAR method CoMFA ( comparative molecular field analysis) was used to study the ent-kauranoids on cytotoxicity in vitro agsinst k562 cells and leaded to one CoMFA models of these data. The Crossvalidated coefficient q2of one model reached 0.561, the non-crossvalidated coefficient r2was up to 0.999, standard deviation was 0.029. CONCLUSION: In the series of ent-kauranoids the CoMFA models reveal the relationship between their bioactivities and structures, these results are helpful to the further design work to find new natural drugs and lead compound with higher bioactivity.

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Quantitative Structure–Activity Relationships of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents

Molecules ◽

10.3390/molecules26175249 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5249

Author(s):

Friederike M. Wunsch ◽

Bernhard Wünsch ◽

Freddy A. Bernal ◽

Thomas J. Schmidt

Keyword(s):

3D Qsar ◽

Structure Activity Relationship ◽

Structural Features ◽

Field Analysis ◽

Activity Relationship ◽

Quantitative Structure ◽

Qsar Study ◽

Activity Data ◽

Structure Activity

On the basis of the finding that various aminoalkyl-substituted chromene and chromane derivatives possess strong and highly selective in vitro bioactivity against Plasmodium falciparum, the pathogen responsible for tropical malaria, we performed a structure–activity relationship study for such compounds. With structures and activity data of 52 congeneric compounds from our recent studies, we performed a three-dimensional quantitative structure–activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) approach as implemented in the Open3DQSAR software. The resulting model displayed excellent internal and good external predictive power as well as good robustness. Besides insights into the molecular interactions and structural features influencing the antiplasmodial activity, this model now provides the possibility to predict the activity of further untested compounds to guide our further synthetic efforts to develop even more potent antiplasmodial chromenes/chromanes.

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

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2020.ajomc-p289 ◽

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.

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3D-QSAR Studies of S-DABO Derivatives as Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180810112321 ◽

2019 ◽

Vol 16 (8) ◽

pp. 868-881

Author(s):

Yueping Wang ◽

Jie Chang ◽

Jiangyuan Wang ◽

Peng Zhong ◽

Yufang Zhang ◽

...

Keyword(s):

Reverse Transcriptase ◽

Three Dimensional ◽

Predictive Ability ◽

3D Qsar ◽

Binding Mode ◽

Quantitative Structure Activity Relationship ◽

Field Analysis ◽

Reverse Transcriptase Inhibitors ◽

Qsar Studies ◽

Hiv 1

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

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3D-QSAR Studies on a Series of 2,4-Thiazolidinedione Derivatives: A Self- Organizing Molecular Field Analysis Approach to Design Novel PTP 1B Inhibitors

Medicinal Chemistry ◽

10.2174/1573406411309060007 ◽

2013 ◽

Vol 9 (6) ◽

pp. 828-845 ◽

Cited By ~ 1

Author(s):

Priyanka Malla ◽

Manoj Kumar

Keyword(s):

3D Qsar ◽

Field Analysis ◽

Molecular Field ◽

Analysis Approach ◽

Qsar Studies ◽

Molecular Field Analysis ◽

Ptp 1B ◽

Self Organizing

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Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

Current Computer - Aided Drug Design ◽

10.2174/1573409915666181221114107 ◽

2020 ◽

Vol 16 (2) ◽

pp. 155-166

Author(s):

Naveen Dhingra ◽

Anand Kar ◽

Rajesh Sharma

Keyword(s):

Three Dimensional ◽

3D Qsar ◽

Docking Study ◽

Structure Activity Relationship ◽

Docking Studies ◽

Activity Relationship ◽

Structural Requirement ◽

Ligand Interaction ◽

Microtubule Polymerization ◽

Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

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Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200627212128 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1714-1721

Author(s):

Hatem A. Abuelizz ◽

El Hassane Anouar ◽

Mohamed Marzouk ◽

Mizaton H. Hasan ◽

Siti R. Saleh ◽

...

Keyword(s):

Molecular Docking ◽

Kojic Acid ◽

Docking Studies ◽

Breast Adenocarcinoma ◽

Amino Acid Residues ◽

New Class ◽

Structure Activity ◽

Tyrosinase Inhibitors ◽

Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

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