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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume34
Issue number1
Early online date26 Oct 2018
DOIs
Accepted/In press30 Aug 2018
E-pub ahead of print26 Oct 2018
Published2019

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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.

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