Structural and chemical basis for enhanced affinity to a series of mycobacterial thymidine monophosphate kinase inhibitors: fragment-based QSAR and QM/MM docking studies

2012 ◽  
Vol 19 (1) ◽  
pp. 179-192 ◽  
Author(s):  
Renata V. Bueno ◽  
Ney R. Toledo ◽  
Bruno J. Neves ◽  
Rodolpho C. Braga ◽  
Carolina H. Andrade
Keyword(s):  
Kinase Inhibitors ◽  
Docking Studies ◽  
Chemical Basis ◽  
Thymidine Monophosphate

Exploring Pyrimidine Pharmacophore as Thymidine Monophosphate Kinase Inhibitors for Antitubercular Activity: A Review

2016 ◽  
Vol 16 (28) ◽  
pp. 3211-3223 ◽  
Author(s):  
Trupti Sameer Chitre ◽  
Kalyani Dhirendra Asgaonkar ◽  
Shital Manoj Patil ◽  
Muthu Kumaradoss Kathiravan ◽  
Subhash Balkrishna Padhye
Keyword(s):  
Kinase Inhibitors ◽  
Antitubercular Activity ◽  
Thymidine Monophosphate

Thymidine (monophosphate) analogues as Mycobacterium tuberculosis thymidylate kinase inhibitors

2002 ◽  
Author(s):  
Philippe Van Rompaey ◽  
Vanheusden Veerle ◽  
Sylvie Pochet ◽  
Hélene Munier-Lehmann ◽  
Matheus Froeyen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Kinase Inhibitors ◽  
Thymidylate Kinase ◽  
Thymidine Monophosphate

scholarly journals Computational evaluation of potent 2-(1H-imidazol-2-yl) pyridine derivatives as potential V600E-BRAF inhibitors

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Abdullahi Bello Umar ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Acquired Resistance ◽  
Docking Studies ◽  
Major Protein ◽  
Pharmacological Properties ◽  
Braf Inhibitors ◽  
Protein Target ◽  
Computational Evaluation ◽  
Better Than

Abstract Background V600E-BRAF is a major protein target involved in various types of human cancers. However, the acquired resistance of the V600E-BRAF kinase to the vemurafenib and the side effects of other identified drugs initiate the search for efficient inhibitors. In the current paper, virtual docking screening combined with drug likeness and ADMET properties predictions were jointly applied to evaluate potent 2-(1H-imidazol-2-yl) pyridines as V600E-BRAF kinase inhibitors. Results Most of the studied compounds showed better docking scores and favorable interactions with theiV600E-BRAF target. Among the screened compounds, the two most potent (14 and 30) with good rerank scores (−124.079 and − 122.290) emerged as the most effective, and potent V600E-BRAF kinase inhibitors which performed better than vemurafenib (−116.174), an approved V600E-BRAF kinase inhibitor. Thus, the docking studies exhibited that these compounds have shown competing inhibition of V600E-BRAF kinase with vemurafenib at the active site and revealed better pharmacological properties based on Lipinski’s and Veber’s drug-likeness rules for oral bioavailability and ADMET properties. Conclusion The docking result, drug-likeness rules, and ADMET parameters identified compounds (14 and 30) as the best hits against V600E-BRAF kinase with better pharmacological properties. This suggests that these compounds may be developed as potent V600E-BRAF inhibitors.

scholarly journals (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

2021 ◽  
Vol 17 ◽  
pp. 2260-2269
Author(s):  
Luiz Claudio Ferreira Pimentel ◽  
Lucas Villas Boas Hoelz ◽  
Henayle Fernandes Canzian ◽  
Frederico Silva Castelo Branco ◽  
Andressa Paula de Oliveira ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Competitive Inhibition ◽  
Leukemia Cell ◽  
Docking Studies ◽  
Leukemia Cell Line ◽  
Inhibition Mechanism ◽  
Triazole Derivatives

The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies.

Dibenzepinones, dibenzoxepines and benzosuberones based p38α MAP kinase inhibitors: Their pharmacophore modelling, 3D-QSAR and docking studies

2019 ◽  
Vol 110 ◽  
pp. 175-185 ◽  
Author(s):  
Mohemmed Faraz Khan ◽  
Garima Verma ◽  
Perwez Alam ◽  
Mymoona Akhter ◽  
Md Afroz Bakht ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
3D Qsar ◽  
Docking Studies ◽  
Pharmacophore Modelling ◽  
P38α Map Kinase

scholarly journals Kinase Inhibitors of Novel Pyridopyrimidinone Candidates: Synthesis and In Vitro Anticancer Properties

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Nagy M. Khalifa ◽  
Mohamed A. Al-Omar ◽  
Hamad M. Alkahtani ◽  
Ahmed H. Bakheit
Keyword(s):  
Kinase Inhibitors ◽  
Human Cancer ◽  
Ethyl Cyanoacetate ◽  
Diethyl Malonate ◽  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Braf V600e ◽  
Kinase Assay ◽  
Human Cancer Cell Lines

A new class of pyridopyrimidinone compounds containing different nitrogenous heterocycles were synthesized starting from the key precursor 2-hydrazinyl-5-phenyl-7-(pyridin-3-yl)pyrido[2,3-d]pyrimidin-4(3H)-one via condensation with series of aromatic aldehydes and cyclization using different reagents as ethyl acetoacetate, ethyl cyanoacetate, diethyl malonate, and ammonium isothiocyanate. The bioassay results showed compound 6 to be highly effective towards three human cancer cell lines (HepG2, PC-3, and HCT-116) in vitro with promising activity values (IC50: 0.5 μM) relative to the standard doxorubicin (IC50: 0.6 μM). Kinase inhibitory evaluation of compound 6 displays hopeful inhibitory action against BRAF V600E, EGFR, and PDGFRβ at100 μM. The molecular docking studies supported the initial kinase assay.

Ligand-based pharmacophore detection, screening of potential pharmacophore and docking studies, to get effective glycogen synthase kinase inhibitors

2013 ◽  
Vol 22 (11) ◽  
pp. 5504-5535 ◽  
Author(s):  
Ritesh Agrawal ◽  
Pratima Jain ◽  
Subodh Narayan Dikshit ◽  
Radhe Shyam Bahare ◽  
Swastika Ganguly
Keyword(s):  
Kinase Inhibitors ◽  
Glycogen Synthase ◽  
Docking Studies ◽  
Glycogen Synthase Kinase
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