scholarly journals 3D QSAR of Pyrrolo Pyrimidine and Thieno Pyrimidines as Human Thymidylate Synthase Inhibitors

2012 ◽  
Vol 9 (4) ◽  
pp. 1699-1710 ◽  
Author(s):  
K. Meena Kumari ◽  
L. Yamini ◽  
M. Vijjulatha
Keyword(s):  
Thymidylate Synthase ◽  
Rational Design ◽  
Cross Validation ◽  
3D Qsar ◽  
Structure Activity ◽  
Dna Biosynthesis ◽  
Contour Plots ◽  
Leave One Out ◽  
Thieno Pyrimidine ◽  
Relationship Of

Thymidylate synthase (TS) is a crucial enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. We report 3D-QSAR analyses on pyrrolo pyrimidine and thieno pyrimidine antifolates to contemplate the mechanism of action and structure-activity relationship of these molecules. By applying leave-one-out (LOO) cross-validation study, cross-validated q2value of 0.523 and 0.566 for CoMFA Ligand based (LB) and Receptor based (RB), 0.516 and 0.471 for CoMSIA LB and RB respectively. while the non-cross-validated r2values were found to be 0.974 and 0.969 for CoMFA LB and RB, 0.983 and 0.972 for CoMSIA LB and RB respectively. The models were graphically interpreted using CoMFA and CoMSIA contour plots. The results obtained from this study were used for rational design of potent inhibitors against thymidylate synthase.

scholarly journals TDPBP Derivative Aiding Liquid-Phase Synthesis Strategy and ACE Inhibitory Structure-activity Relationship of Anti-SARS Octapeptide

2020 ◽  
Author(s):  
Haidi Li ◽  
Jin Ren ◽  
Zixin Zhang ◽  
Junyou Li ◽  
Ninghui Chang ◽  
...  
Keyword(s):  
Liquid Phase ◽  
3D Qsar ◽  
Ace Inhibition ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Phase Synthesis ◽  
Fmoc Chemistry ◽  
Structure Activity ◽  
Synthesis Strategy ◽  
Relationship Of

The tri(4'-diphenylphosphonyloxylbenzoyl phenyl) phosphate (TDPBP) derivatives were designed and developed as C-terminal supports to aid the greener and highefficient liquid-phase peptide synthesis (LPPS) without the need of unrecyclable resin and chromatographic separation, whereby the anti-SARS octapeptide (2) (AVLQSGFR) was synthesized with TDPBP-OH support via Fmoc chemistry and support-aided precipitation (SAP) technology. Furthermore, the ACE inhibition and the inhibitory structure-activity relationship (SAR) between the synthetic C-terminal amidated derivate (1), anti-SARS octapeptide (2) and its alanine-scanning sequence analogues (3) to (9) were systematically studied by HPLC analysis and 3D-QSAR via molecular docking.<br>

scholarly journals Structure–Activity Relationship of Phytotoxic Natural 10-Membered Lactones and Their Semisynthetic Derivatives

2021 ◽  
Vol 7 (10) ◽  
pp. 829
Author(s):  
Anna Dalinova ◽  
Anatoly Fedorov ◽  
Vsevolod Dubovik ◽  
Olga Voitsekhovskaja ◽  
Elena Tyutereva ◽  
...  
Keyword(s):  
Rational Design ◽  
Fungicidal Activity ◽  
Structural Features ◽  
Hydroxyl Group ◽  
High Yield ◽  
Sf9 Cells ◽  
Structure Activity ◽  
Relationship Of ◽  
Derivatives Of ◽  
Target Activity

Ten-membered lactones (nonenolides) demonstrate phytotoxic, antimicrobial, and fungicidal activity promising for the development of natural product-derived pesticides. The fungus Stagonospora cirsii is able to produce phytotoxic stagonolides A (1), J (2), K (3) and herbarumin I (4) with high yield. The aim of this study was to create a set of structurally related nonenolides and to reveal the structural features that affect their biological activity. Stagonolide A (1) and C-7 oxidized stagonolide K (11) showed the highest phytotoxicity in leaf puncture assay and agar seedlings assay. The oxidation of C-7 hydroxyl group (as in 1, acetylstagonolide A (10) and (11) led to the manifestation of toxicity to microalgae, Bacillus subtilis and Sf9 cells regardless of the configuration of C-9 propyl chains (R in 1 and 10, S in 11). C-7 non-oxidized nonenolides displayed none or little non-target activity. Notably, 7S compounds were more phytotoxic than their 7R analogues. Due to the high inhibitory activity against seedling growth and the lack of side toxicity, mono- and bis(acetyl)- derivatives of herbarumin I were shown to be potent for the development of pre-emergent herbicides. The identified structural features can be used for the rational design of new herbicides.

scholarly journals Structure Activity Relationships, QSAR Modeling and Drug-Like Calculations of TP Inhibition of 1,3,4-Oxadiazoline-2-Thione Derivatives

2014 ◽  
Vol 37 ◽  
pp. 113-124 ◽  
Author(s):  
Zineb Almi ◽  
Salah Belaidi ◽  
Touhami Lanez ◽  
Noureddine Tchouar
Keyword(s):  
Predictive Power ◽  
Cross Validation ◽  
Molecular Descriptor ◽  
Qsar Model ◽  
Qsar Modeling ◽  
Qsar Studies ◽  
Structure Activity ◽  
Qsar Models ◽  
Leave One Out

QSAR studies have been performed on twenty-one molecules of 1,3,4-oxadiazoline-2-thiones. The compounds used are among the most thymidine phosphorylase (TP) inhibitors. A multiple linear regression (MLR) procedure was used to design the relationships between molecular descriptor and TP inhibition of the 1,3,4-oxadiazoline-2-thione derivatives. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based of the following descriptors: logP, HE, Pol, MR, MV, and MW, qO1, SAG, for the TP inhibitory activity. To confirm the predictive power of the models, an external set of molecules was used. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR models.

scholarly journals 3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuwei Wang ◽  
Yifan Guo ◽  
Shaojia Qiang ◽  
Ruyi Jin ◽  
Zhi Li ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rational Design ◽  
Binding Free Energy ◽  
3D Qsar ◽  
Md Simulations ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Anthraquinone Derivatives

PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.

Sign in / Sign up

Export Citation Format

Share Document