scholarly journals Modeling the Antileukemia Activity of Ellipticine-Related Compounds: QSAR and Molecular Docking Study

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 24 ◽  
Author(s):  
Edgar Márquez ◽  
José R. Mora ◽  
Virginia Flores-Morales ◽  
Daniel Insuasty ◽  
Luis Calle
Keyword(s):  
Molecular Structure ◽  
Binding Free Energy ◽  
Docking Study ◽  
Quantitative Structure Activity Relationship ◽  
Quantitative Structure ◽  
Molecular Docking Study ◽  
Modeling Simulation ◽  
Structure Activity ◽  
Related Compounds ◽  
Cancer Activity

The antileukemia cancer activity of organic compounds analogous to ellipticine representes a critical endpoint in the understanding of this dramatic disease. A molecular modeling simulation on a dataset of 23 compounds, all of which comply with Lipinski’s rules and have a structure analogous to ellipticine, was performed using the quantitative structure activity relationship (QSAR) technique, followed by a detailed docking study on three different proteins significantly involved in this disease (PDB IDs: SYK, PI3K and BTK). As a result, a model with only four descriptors (HOMO, softness, AC1RABAMBID, and TS1KFABMID) was found to be robust enough for prediction of the antileukemia activity of the compounds studied in this work, with an R2 of 0.899 and Q2 of 0.730. A favorable interaction between the compounds and their target proteins was found in all cases; in particular, compounds 9 and 22 showed high activity and binding free energy values of around −10 kcal/mol. Theses compounds were evaluated in detail based on their molecular structure, and some modifications are suggested herein to enhance their biological activity. In particular, compounds 22_1, 22_2, 9_1, and 9_2 are indicated as possible new, potent ellipticine derivatives to be synthesized and biologically tested.

scholarly journals SYNTHESIS, MOLECULAR MODELING, AND QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP STUDIES OF UNDEC-10-ENEHYDRAZIDE DERIVATIVES AS ANTIMICROBIAL AGENTS

2017 ◽  
Vol 10 (16) ◽  
pp. 94
Author(s):  
Manju Kumari ◽  
Rakesh Narang ◽  
Surendra Kumar Nayak ◽  
Sachin Kumar Singh ◽  
Vivek Gupta ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Quantitative Structure Activity Relationship ◽  
Side Chain ◽  
Quantitative Structure ◽  
Molecular Docking Study ◽  
Qsar Studies ◽  
Structure Activity ◽  
Methoxy Groups

Objective: In recent years, an increasing frequency and severity of antimicrobial resistance to different antimicrobial agents, demands new remedies for the treatment of infections. Therefore, in this study, a series of undec-10-enehydrazide derivatives were synthesized and screened for in vitro activity against selected pathogenic microbial strains.Methods: The synthesis of the intermediate and target compounds was performed by standard procedure. Synthesized compounds were screened for antimicrobial activity by tube dilution method. Molecular docking study of synthesized derivatives was also performed to find out their interaction with the target site of β-ketoacyl-acyl carrier protein synthase III, (FabH; pdb id:3IL7) by docking technique. Quantitative structure–activity relationship (QSAR) studies were also performed to correlate antimicrobial activity with structural properties of synthesized molecules.Results: Antimicrobial screening results showed that compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3-flourophenyl)-4-oxoazetidine moiety was found to be most potent. QSAR studies revealed the importance of Randic topology parameter (R) in describing the antimicrobial activity of synthesized derivatives. Molecular docking study indicated hydrophobic interaction of deeply inserted aliphatic side chain of the ligand with FabH. The N-atoms of hydrazide moiety interacts with Ala246 and Asn247 through H-bonding. The m- and p-methoxy groups form H-bond with water and side chain of Arg36, respectively.Conclusion: Compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3- flourophenyl)-4-oxoazetidine moiety was found to most potent antibacterial and antifungal compounds, respectively.

Biological Activity, Physical Properties, and Toxicity

2021 ◽  
Vol 6 (3) ◽  
pp. 25-34
Author(s):  
Ranita Pal ◽  
Pratim Kumar Chattaraj
Keyword(s):  
Molecular Structure ◽  
Biological Activity ◽  
Molecular Biology ◽  
Drug Design ◽  
Physical Properties ◽  
Quantitative Structure Activity Relationship ◽  
Molecular Properties ◽  
Quantitative Structure ◽  
Qsar Analysis ◽  
Structure Activity

In the current pandemic-stricken world, quantitative structure-activity relationship (QSAR) analysis has become a necessity in the domain of molecular biology and drug design, realizing that it helps estimate properties and activities of a compound, without actually having to spend time and resources to synthesize it in the laboratory. Correlating the molecular structure of a compound with its activity depends on the choice of the descriptors, which becomes a difficult and confusing task when we have so many to choose from. In this mini-review, the authors delineate the importance of very simple and easy to compute descriptors in estimating various molecular properties/toxicity.

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