Docking field‐based <scp>QSAR</scp> and pharmacophore studies on the substituted pyrimidine derivatives targeting <scp>HIV</scp>‐1 reverse transcriptase

Fan, Ningning; Zhang, Shuang; Sheng, Tao; Zhao, Liang; Liu, Zhenming; Liu, Junyi; Wang, Xiaowei

doi:10.1111/cbdd.13086

Cited by 10 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Four features were generated from the Gaussian field analysis, each representing different properties such as lipophilic, electronegative, electropositive, steric, and hydrogen bond acceptors. These features were visualized with different colors, indicating the substituent effects on the regions and whether they enhance or decrease the compound’s biological activity [ 15 , 16 , 17 ]. The results of the most statistically significant model (model 4) are summarized in Table 5 .…”

Section: Resultsmentioning

confidence: 99%

Cantharidin-Based Verbenone Derivatives as a Novel Insecticide against Plutella xylostella: Design, Synthesis, Insecticidal Activity Evaluation, and 3D QSAR Study

Lee,

Nada,

Kim

et al. 2023

Biomolecules

View full text Add to dashboard Cite

The diamondback moth is a detrimental insect pest of brassicaceous crops which was among the first crop insects to be reported as DDT resistant. It has since proven to be significantly resistant to nearly every synthetic insecticide used in the field in many crucifer-producing regions. Due to insecticide control failures in some parts of the world, economically viable crucifer production is now all but impossible. As a result, there has been an increasing effort to identify new compounds with strong pesticidal activity. Cantharidin is one such compound that has been shown to be highly effective against a variety of insect pests. However, its chemical synthesis and potential toxicity to non-target organisms have been a major source of concern. Herein, using rational design approaches, a new series of cantharidin-based verbenone derivatives were synthesized and evaluated for their insecticidal activities against the diamondback moth. Among different compounds screened, compounds 6a, 6h, 6i, and 6q emerged as the most potent compounds exhibiting 100% mortality at a concentration of 100 mg/L after four days. These compounds demonstrated a good anti-feeding effect against the diamondback moth on cabbage leaves. Subsequently, a 3D QSAR study was carried out to identify the key structural features of the synthesized compounds and their correlation with insecticidal activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Cantharidin-Based Verbenone Derivatives as a Novel Insecticide against Plutella xylostella: Design, Synthesis, Insecticidal Activity Evaluation, and 3D QSAR Study

Lee,

Nada,

Kim

et al. 2023

Biomolecules

View full text Add to dashboard Cite

show abstract

“…The average RMSD descriptor of all the docked compounds were calculated to corroborate their stability in biological system [ 28 , 29 , 30 ]. As the justified threshold for RMSD calculation is 2 Å, its mean average RMSD value of all the complexes less than this threshold provides us with the proof that our docking process is validated, as having RMSD for anti-cancer docking protocol 2.0 Å, for anti-diabetic 1.35 Å and for anti-oxidant 0.71 Å [ 31 , 32 , 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

et al. 2021

View full text Add to dashboard Cite

Objective: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. Methodology: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. Results: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

show abstract

“…The ‘Epik’ module (V 5.4, Schrödinger, LLC, NY 2020) was used for generating possible ionisation states for each ligand at pH = 7.0 ± 0.0. For our entire ligand preparation protocols, we adhered to OPLS-2005 force field 28 .…”

Section: Methodsmentioning

confidence: 99%

Identification of hydantoin based Decaprenylphosphoryl-β-d-Ribose Oxidase (DprE1) inhibitors as antimycobacterial agents using computational tools

Mali

Pandey

Bhandare

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Tuberculosis (TB) is one of the emerging infectious diseases in the world. DprE1 (Decaprenylphosphoryl-β-d-ribose 2′-epimerase), an enzyme accountable for mycobacterial cell wall synthesis was the first drug gable target based on discoveries of inhibitors via HTS (high throughput screening). Since then, many literature reports have been published so far enlightening varieties of chemical scaffolds acting as inhibitors of DprE1. Herein, in our present study, we have developed statistically robust GA-MLR (genetic algorithm multiple linear regression), atom-based as well as field based-3D-QSAR models. Both atom-based as well as field based-3D-QSAR models (internally as well as externally validated) were obtained with robust Training set, R2 > 0.69 and Test set, Q2 > 0.50. We have also developed top ranked 5 point hypothesis AAAHR_1 among 14 CPHs (common pharmacophore hypotheses). We found that our dataset molecule had more docking score (XP mode = − 9.068 kcal/mol) than the standards isoniazid and ethambutol; when docked into binding pockets of enzyme 4P8C with Glide module. We further queried our best docked dataset molecule 151 for ligand based virtual screening using “SwissSimilarity” platform. Among 9 identified hits, we found ZINC12196803 had best binding energies and docking score (docking score = − 9.437 kcal/mol, MMGBSA dgBind = − 70.508 kcal/mol). Finally, our molecular dynamics studies for 1.2–100 ns depicts that these complexes are stable. We have also carried out in-silico ADMET predictions, Cardiac toxicity, ‘SwissTargetPredictions’ and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding energy calculations for further explorations of dataset as well as hit molecules. Our current studies showed that the hit molecule ZINC12196803 may enlighten the path for future developments of DprE1 inhibitors.

show abstract

Docking field‐based QSAR and pharmacophore studies on the substituted pyrimidine derivatives targeting HIV‐1 reverse transcriptase

Cited by 10 publications

References 26 publications

Cantharidin-Based Verbenone Derivatives as a Novel Insecticide against Plutella xylostella: Design, Synthesis, Insecticidal Activity Evaluation, and 3D QSAR Study

Cantharidin-Based Verbenone Derivatives as a Novel Insecticide against Plutella xylostella: Design, Synthesis, Insecticidal Activity Evaluation, and 3D QSAR Study

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Identification of hydantoin based Decaprenylphosphoryl-β-d-Ribose Oxidase (DprE1) inhibitors as antimycobacterial agents using computational tools

Contact Info

Product

Resources

About