Identification and validation of novel microtubule suppressors with an imidazopyridine scaffold through structure-based virtual screening and docking

Elseginy, Samia A.; Oliveira, A. Sofia F.; Shoemark, Deborah K.; Sessions, Richard B.

doi:10.1039/d1md00392e

Cited by 9 publications

(2 citation statements)

References 56 publications

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“…The relation between potency, pharmacokinetics, and toxicity is very crucial for the drug efficiency. Using pkCSM [48], Swiss ADME [49], and Data Warrior [48,50], the pharmacokinetics (absorption, distribution, metabolism, and excretion), drug-likeness, and toxicity features of the chemical compound 8 were assessed in this investigation. For a medicine to work effectively, potency, pharmacokinetics, and toxicity must interact.…”

Section: Admet Analysismentioning

confidence: 99%

Development of a New Benzofuran–Pyrazole–Pyridine-Based Molecule for the Management of Osteoarthritis

Abd El-Karim,

Mahmoud,

Al-Mokaddem

et al. 2023

Molecules

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Osteoarthritis is a substantial burden for patients with the disease. The known medications for the disease target the mitigation of the disease’s symptoms. So, drug development for the management of osteoarthritis represents an important challenge in the medical field. This work is based on the development of a new benzofuran–pyrazole–pyridine-based compound 8 with potential anti-inflammatory and anti-osteoarthritis properties. Microanalytical and spectral data confirmed the chemical structure of compound 8. The biological assays indicated that compound 8 produces multifunctional activity as an anti-osteoarthritic candidate via inhibition of pro-inflammatory mediators, including RANTES, CRP, COMP, CK, and LPO in OA rats. Histopathological and pharmacokinetic studies confirmed the safety profile of the latter molecule. Accordingly, compound 8 is considered a promising anti-osteoarthritis agent and deserves deeper investigation in future trials.

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Section: Admet Analysismentioning

confidence: 99%

Development of a New Benzofuran–Pyrazole–Pyridine-Based Molecule for the Management of Osteoarthritis

Abd El-Karim,

Mahmoud,

Al-Mokaddem

et al. 2023

Molecules

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“…Eg5 inhibitors are characterised by their selectivity and safety, because Eg5 functions only during mitosis; and does not affect the non-proliferative cells, which renders Eg5 inhibitors as selective inhibitors [ 8 ]. In addition, Eg5 does not induce neuropathic side effects, which are found with microtubules inhibitors, due to the absence of the Eg5 protein in the adult peripheral nervous system [ 9 , 10 ]. The literature review revealed that Eg5 inhibitors are divided into two groups, according to their mechanism of action within the Eg5 protein [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Identifying and characterising promising small molecule inhibitors of kinesin spindle protein using ligand-based virtual screening, molecular docking, molecular dynamics and MM‑GBSA calculations

Elseginy

2024

J Comput Aided Mol Des

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The kinesin spindle protein (Eg5) is a mitotic protein that plays an essential role in the formation of the bipolar spindles during the mitotic phase. Eg5 protein controls the segregation of the chromosomes in mitosis which renders it a vital target for cancer treatment. In this study our approach to identifying novel scaffold for Eg5 inhibitors is based on targeting the novel allosteric pocket (α4/α6/L11). Extensive computational techniques were applied using ligand-based virtual screening and molecular docking by two approaches, MOE and AutoDock, to screen a library of commercial compounds. We identified compound 8-(3-(1H-imidazol-1-ylpropylamino)-3-methyl-7-((naphthalen-3-yl)methyl)-1H-purine-2, 6 (3H,7H)-dione (compound 5) as a novel scaffold for Eg5 inhibitors. This compound inhibited cancer cell Eg5 ATPase at 2.37 ± 0.15 µM. The molecular dynamics simulations revealed that the identified compound formed stable interactions in the allosteric pocket (α4/α6/L11) of the receptor, indicating its potential as a novel Eg5 inhibitor. Graphical Abstract

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Imidazo[1,2-a]Pyridine Derivatives–Copper(II) Salts: Highly Effective In Situ Combination for Catecholase

et al. 2023

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Identification and validation of novel microtubule suppressors with an imidazopyridine scaffold through structure-based virtual screening and docking

Abstract: Targeting the colchicine binding site of α/β tubulin microtubules can lead to suppression of microtubule dynamics, cell cycle arrest and apoptosis. Therefore, the development of microtubule (MT) inhibitors is considered...

Cited by 9 publications

References 56 publications

Development of a New Benzofuran–Pyrazole–Pyridine-Based Molecule for the Management of Osteoarthritis

Development of a New Benzofuran–Pyrazole–Pyridine-Based Molecule for the Management of Osteoarthritis

Identifying and characterising promising small molecule inhibitors of kinesin spindle protein using ligand-based virtual screening, molecular docking, molecular dynamics and MM‑GBSA calculations

Imidazo[1,2-a]Pyridine Derivatives–Copper(II) Salts: Highly Effective In Situ Combination for Catecholase

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