An analogue of a kinase inhibitor exhibits subjective characteristics that contribute to its inhibitory activities as a potential anti-cancer candidate: insights through computational biomolecular modelling of UM-164 binding with lyn protein

Ndagi, Umar; Abdullahi, Maryam; Hamza, Asmau; Soliman, Mahmoud E. S.

doi:10.1039/c9ra07204g

Cited by 11 publications

(8 citation statements)

References 54 publications

(112 reference statements)

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“…UM-164: The active substance is a highly powerful dual c-Src/p38 inhibitor that inhibits both p38 and p38 and has a binding constant Kd of 2.7 nM for c-Src. The drug is the subject of a great deal of research since it claims to be able to cure triple-negative breast cancer [56].…”

Section: Srt2104 (Gsk2245840)mentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

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For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor–acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

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Section: Srt2104 (Gsk2245840)mentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

View full text Add to dashboard Cite

show abstract

“…The effect of the overall motion of protein due to ligands attachment was analyzed by PCA using the construction of eigenvectors. PCA is a powerful method used for determining the rigidity of each atom and largescale motions during MD simulation (Ndagi et al, 2020). Figure 8 displays the conformational sampling of WT and V27F ASNase in the required subspace by projecting the Cα atom along eigenvectors 1 and 2.…”

Section: Principal Component Analysismentioning

confidence: 99%

Development of Escherichia coli asparaginase II for the Treatment of Acute Lymphocytic Leukemia: In Silico Reduction of asparaginase II Side Effects by a Novel Mutant (V27F)

Ardalan

Sepahi

Khavari-Nejad

2021

Asian Pac J Cancer Prev

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Acute lymphoblastic leukemia (ALL) is a common blood disease in children that is accountable for many deaths. Due to major improvements in treatment procedures in the past 50 years, the survivability of this disease has risen dramatically to about 90 percent today. L-asparaginase (ASNase) has been used to treat ALL. The glutaminase (GLNase) activity of this enzyme causes some side effects and is unnecessary for anticancer activity. This study investigated mutagenesis in Escherichia coli ASNase II to find a mutant with lower GLNase activity via molecular dynamics (MD) simulation. Residues with low binding energy to asparagine (Asn) and high binding energy to glutamine (Gln) were chosen for mutagenesis. A mutant with low free binding energy to Gln was then selected for molecular docking and MD studies. The results showed that V27F is a good candidate for reducing GLNase activity and that it has little effect on enzyme ASNase activity. A simulation analysis showed that the V27F mutant was more stable than the WT ASNase and that mutagenesis was quite successful.

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“…Before the replacement of missing residues from the loop, the ligand was separated from the protein except for two magnesium atoms. Only chain A was used for docking to reduce computational cost (Ndagi et al, 2020).…”

Section: Screening Of Drug‐like Libraries Against Tubercular Aminoacyl‐trna Synthasesmentioning

confidence: 99%

A consequence of drug targeting of aminoacyl‐tRNA synthetases in Mycobacteriumtuberculosis

2021

Self Cite

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Drug‐resistant Mycobacterium tuberculosis poses a great threat to public health and remains one of the red‐flag tagged infectious diseases, with the tendency of comorbidity with other disease conditions such as HIV/AIDS. This perhaps is responsible for redoubling of effort in tuberculosis research and continuous change in patient management to optimize the drug therapy. Aminoacyl‐tRNA synthetases are essential enzymes in M. tuberculosis that catalyse the transfer of a particular amino acid to its corresponding specific tRNA to form an aminoacyl‐tRNA. These enzymes are believed to be novel antibacterial, antifungal and antiparasitic drug targets because of their role in the process of protein translation. Therefore, their existence as a compliment of M. tuberculosis has attracted a lot of research interest with the aim of curbing the scourge and provide the most effective drug in the treatment of tuberculosis. This leads to the discovery of a pool of aminoacyl‐tRNA synthetases with their essential inhibitors. This review seeks to articulate the current advances in the development of new TB drugs exhibiting novelty in their mode of action with specific emphasis on aminoacyl‐tRNA synthetases as drug targets.

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An analogue of a kinase inhibitor exhibits subjective characteristics that contribute to its inhibitory activities as a potential anti-cancer candidate: insights through computational biomolecular modelling of UM-164 binding with lyn protein

Abstract: This study provides the first account of the molecular impact of UM-164 binding on lyn protein using various computational approaches.

Cited by 11 publications

References 54 publications

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Development of Escherichia coli asparaginase II for the Treatment of Acute Lymphocytic Leukemia: In Silico Reduction of asparaginase II Side Effects by a Novel Mutant (V27F)

A consequence of drug targeting of aminoacyl‐tRNA synthetases in Mycobacteriumtuberculosis

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