De novo design of N-(pyridin-4-ylmethyl)aniline derivatives as KDR inhibitors: 3D-QSAR, molecular fragment replacement, protein-ligand interaction fingerprint, and ADMET prediction

Zhang, Yanmin; Liu, Haichun; Jiao, Yu; Yuan, Haoliang; Feng-xiao, Wang; Lü, Shan; Yao, Sihui; Ke, Zhipeng; Tai, Wenting; Jiang, Yulei; Chen, Yadong; Lü, Tao

doi:10.1007/s11030-012-9405-y

Cited by 17 publications

(11 citation statements)

References 36 publications

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“…The ellipses define regions where well-absorbed compounds are expected to be found: 95% of well-absorbed compounds are expected to fall within the 95% ellipse, while 99% of wellabsorbed compounds should fall within the 99% ellipse. Note that the location of any particular compound does not necessarily imply whether it will be well, moderately, or poorly absorbed (Paixão et al, 2012;Zhang et al, 2012). In general, however, absorption tends to drop off quite rapidly outside the 95% ellipse.…”

Section: Active Site Subsitementioning

confidence: 99%

In vitro inhibitory effect of Boeserngin A on human acetylcholinerase: understanding its potential using in silico ADMET studies

Abdelwahab¹

2013

J. App. Pharm. Sci.

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Boesenbergia rotunda is a medicinal plant that used traditionally in South East Asia as a healing for various ailments including neurological disorders. Therefore, this research was designed to describe the biological evaluation pertaining to anti-human cholinesterase (hAChE) activities, molecular docking and in silico prediction of Boesenbergin A (BA), a natural chalcone isolated from B. rotunda. The anti-hAChE activity of BA was evaluated using acetylthiocholine as a substrate and 5,5-dithiobis[2-nitrobenzoic acid] (DTNB) as chromogen. Docking study with flexible boesenbergin A was done using Autodock 4.2 software and A Lamarkian Genetic Algorithm search method. ADME/Tox analysis was also performed using ADMET Descriptors software. The inhibitory activities of BA and the standard drugs tacrin and propidium iodide on human acetylcholinesterase are 70.1±5.43, 76.6±5.11 and 28.2±2.47, respectively. Molecular docking investigation showed that BA occupies the active site of hAChE and this strongly suggests that it acts as a competitive inhibitor and ultimately reduces the activity of the enzyme. BA also exhibited good ADMET properties indicating capacity for further studies towards developing this compound into a potent drug candidate for the treatment of Alzheimer's disease. The present study extends the understanding on the molecular mechanism underlying the diverse biological activities of Boesenbergia rotunda.

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Section: Active Site Subsitementioning

confidence: 99%

In vitro inhibitory effect of Boeserngin A on human acetylcholinerase: understanding its potential using in silico ADMET studies

Abdelwahab¹

2013

J. App. Pharm. Sci.

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“…In this study, 3D-QSAR models were developed using CoMFA [20] and CoMSIA [21] technology based on 85 2-difluoromethylbenzimidazole derivatives [22][23][24]. The relationships between the key structural and pharmacodynamic information were obtained from the 3D-QSAR model, which were helpful for further drug research [25][26][27][28][29][30]. The binding mode of the compound 29 with 4YKN was explored through molecular docking and molecular dynamics simulation.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors

et al. 2022

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PI3Kα is one of the potential targets for novel anticancer drugs. In this study, a series of 2-difluoromethylbenzimidazole derivatives were studied based on the combination of molecular modeling techniques 3D-QSAR, molecular docking, and molecular dynamics. The results showed that the best comparative molecular field analysis (CoMFA) model had q2 = 0.797 and r2 = 0.996 and the best comparative molecular similarity indices analysis (CoMSIA) model had q2 = 0.567 and r2 = 0.960. It was indicated that these 3D-QSAR models have good verification and excellent prediction capabilities. The binding mode of the compound 29 and 4YKN was explored using molecular docking and a molecular dynamics simulation. Ultimately, five new PI3Kα inhibitors were designed and screened by these models. Then, two of them (86, 87) were selected to be synthesized and biologically evaluated, with a satisfying result (22.8 nM for 86 and 33.6 nM for 87).

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“…However, the assessment of phenylpropanoids which has a functional derivative of aryl groups for BCL 2 is still unknown. In this work, we are using virtual platforms screening based on protein structure (structure based) [20,21] and determining the drug-likeness using rules Lipinski [22] where Lipinski is complementary to identify compounds…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of Aryl Eugenol Derivatives as Anti-Colorectal Cancer by Inducing of Apoptosis

Fadilah

Yanuar

Arsianti

et al. 2017

Asian J Pharm Clin Res

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Objective: Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells. Methods:We screened some derivatives aryl eugenol based on their interactions with Bcl-2 in many cancer tissues, using computer software applications (in silico method) to determine the best compounds. The docking experiment on Bcl-2 (Protein Data Bank ID 4LXD) was carried out by suitably positioning the energy-minimized ligand in the active site while carefully monitoring non-bonded interactions of the ligand enzyme. Results:The resulting ligand-receptor complex was docked using the Autodock Vina software. Docking results based free binding energy, EUGACl (21), EUASABr (17), EUGEABr (19), and EUASACL (17), has the lowest binding energy than navitoclax and binds significantly to BCL 2. In silico ADMET predictions revealed that except SA, ASA, and GEA, all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. Conclusion:These compounds of aryl eugenol (17, 19, and 21) may serve as a potential lead compound for developing new anticancer as apoptosis inducers.

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De novo design of N-(pyridin-4-ylmethyl)aniline derivatives as KDR inhibitors: 3D-QSAR, molecular fragment replacement, protein-ligand interaction fingerprint, and ADMET prediction

Cited by 17 publications

References 36 publications

In vitro inhibitory effect of Boeserngin A on human acetylcholinerase: understanding its potential using in silico ADMET studies

In vitro inhibitory effect of Boeserngin A on human acetylcholinerase: understanding its potential using in silico ADMET studies

Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors

In Silico Study of Aryl Eugenol Derivatives as Anti-Colorectal Cancer by Inducing of Apoptosis

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