iVS analysis to evaluate the impact of scaffold diversity in the binding to cellular targets relevant in cancer

Agostino Cilibrizzi; Giuseppe Floresta; Vincenzo Abbate; Maria Paola Giovannoni

doi:10.1080/14756366.2018.1518960

iVS analysis to evaluate the impact of scaffold diversity in the binding to cellular targets relevant in cancer

Agostino Cilibrizzi, Giuseppe Floresta, Vincenzo Abbate, Maria Paola Giovannoni

Research output: Contribution to journal › Article › peer-review

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Abstract

This study reports the application of inverse virtual screening (iVS) methodologies to identify cellular proteins as suitable targets for a library of heterocyclic small-molecules, with potential pharmacological implications. Standard synthetic procedures allow facile generation of these ligands showing a high degree of core scaffold diversity. Specifically, we have computationally investigated the binding efficacy of the new series for target proteins which are involved in cancer pathogenesis. As a result, nine macromolecules demonstrated efficient binding interactions for the molecular dataset, in comparison to the co-crystallised ligand for each target. Moreover, the iVS analysis led us to confirm that 27 analogues have high affinity for one or more examined cellular proteins. The additional evaluation of ADME and drug score for selected hits also highlights their capability as drug candidates, demonstrating valuable leads for further structure optimisation and biological studies.

Original language	English
Pages (from-to)	44-50
Number of pages	7
Journal	JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume	34
Issue number	1
Early online date	26 Oct 2018
DOIs	https://doi.org/10.1080/14756366.2018.1518960
Publication status	Published - 2019

Keywords

Inverse virtual screening
biological targets
heterocycles
scaffold diversity
small-molecules

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/14756366.2018.1518960Licence: CC BY

iVS analysis to evaluate_CILIBRIZZI_Accepted30August2018 GOLD VoR (CC BY)Final published version, 1.16 MBLicence: CC BY

Cite this

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PY - 2019

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iVS analysis to evaluate the impact of scaffold diversity in the binding to cellular targets relevant in cancer

Abstract

Keywords

UN SDGs

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