Molecular principle of the cyclin-dependent kinase selectivity of 4-(thiazol-5-yl)-2-(phenylamino) pyrimidine-5-carbonitrile derivatives revealed by molecular modeling studies

2016 ◽  
Vol 18 (3) ◽  
pp. 2034-2046 ◽  
Author(s):  
Xiaotian Kong ◽  
Huiyong Sun ◽  
Peichen Pan ◽  
Sheng Tian ◽  
Dan Li ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cyclin Dependent Kinase ◽  
Selective Inhibitors ◽  
High Sequence Identity ◽  
Cyclin Dependent Kinases ◽  
Sequence Identity ◽  
Modeling Studies ◽  
Binding Pockets ◽  
Molecular Modeling Studies

Due to the high sequence identity of the binding pockets of cyclin-dependent kinases (CDKs), designing highly selective inhibitors towards a specific CDK member remains a big challenge.

scholarly journals Molecular modeling studies of quinazolinone derivatives as novel PI3Kδ selective inhibitors

RSC Advances ◽  
2017 ◽  
Vol 7 (89) ◽  
pp. 56344-56358 ◽  
Author(s):  
Xiu Xiu Peng ◽  
Kai Rui Feng ◽  
Yu Jie Ren
Keyword(s):  
Molecular Modeling ◽  
Pharmacophore Model ◽  
Modeling Method ◽  
Selective Inhibitors ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Quinazolinone Derivatives

The main molecular modeling method, the docking results of newly designed compoundD04and the best pharmacophore model are reported herein.

scholarly journals Indole-Based Hydrazones Containing A Sulfonamide Moiety as Selective Inhibitors of Tumor-Associated Human Carbonic Anhydrase Isoforms IX and XII

2019 ◽  
Vol 20 (9) ◽  
pp. 2354 ◽  
Author(s):  
Kübra Demir-Yazıcı ◽  
Silvia Bua ◽  
Nurgül Mutlu Akgüneş ◽  
Atilla Akdemir ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Carbonic Anhydrase ◽  
Enzyme Inhibition ◽  
Active Sites ◽  
Selective Inhibitors ◽  
Binding Interactions ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Human Carbonic Anhydrase

Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII over hCA I and II. Six compounds showed KI values lower than 10 nM against hCA IX or XII. Molecular modeling studies were performed to suggest binding interactions between the ligand and the hCA active sites.

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

scholarly journals Evidence for Dual Site Binding of Nile Blue A toward DNA: Spectroscopic, Thermodynamic, and Molecular Modeling Studies

ACS Omega ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 2613-2625
Author(s):  
Mukti Mohammad ◽  
Harun Al Rasid Gazi ◽  
Kumud Pandav ◽  
Prateek Pandya ◽  
Md. Maidul Islam
Keyword(s):  
Molecular Modeling ◽  
Nile Blue ◽  
Nile Blue A ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Dual Site ◽  
Site Binding

Recreational drugs 25I-NBOH and 25I-NBOMe bind to both Sudlow's sites I and II of Human Serum Albumin (HSA): Biophysical and molecular modeling studies

2021 ◽  
Author(s):  
Wellington Alves de Barros ◽  
Marina de Magalhães Silva ◽  
Maria Dayanne de Araújo Dantas ◽  
Josue Santos ◽  
Isis Figueiredo ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Molecular Modelling ◽  
Recreational Drugs ◽  
Modeling Studies ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Molecular Modeling Studies

Experimental, biophysical, and molecular modelling studies between 25I-NBOH and 25I-NBOMe with human serum albumin (HSA) have indicated that these recreational drugs simultaneously bind to site I and II of the...

Sign in / Sign up

Export Citation Format

Share Document