Dataset Information

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 a promising route to anticancer agents. Our approach to identify novel scaffolds as MT inhibitors depends on a 3D-structure-based pharmacophore approach and docking using three programs MOE, Autodock and BUDE (Bristol University Docking Engine) to screen a library of virtual compounds. From this work we identified the compound 7-(3-hydroxy-4-methoxy-phenyl)-3-(3-trifluoromethyl-phenyl)-6,7-dihydro-3H-imidazo[4,5-b]pyridin-5-ol (6) as a novel inhibitor scaffold. This compound inhibited several types of cancer cell proliferation at low micromolar concentrations with low toxicity. Compound 6 caused cell cycle arrest in the G2/M phase and blocked tubulin polymerization at low micromolar concentration (IC₅₀ = 6.1 ±0.1 μM), inducing apoptosis via activation of caspase 9, increasing the level of the pro-apoptotic protein Bax and decreasing the level of the anti-apoptotic protein Bcl2. In summary, our approach identified a lead compound with potential antimitotic and antiproliferative activity.

SUBMITTER: Elseginy SA

PROVIDER: S-EPMC9384815 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Elseginy Samia A SA Oliveira A Sofia F ASF Shoemark Deborah K DK Sessions Richard B RB

RSC medicinal chemistry 20220518 8

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 a promising route to anticancer agents. Our approach to identify novel scaffolds as MT inhibitors depends on a 3D-structure-based pharmacophore approach and docking using three programs MOE, Autodock and BUDE (Bristol University Docking Engine) to screen a library of virtual comp ...[more]

PMID: 36092142

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Dataset Information

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

Publications

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

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