Synthesis and biological activity evaluation of 3-(hetero) arylideneindolin-2-ones as potential c-Src inhibitors

Abstract

Inhibition of c-Src is considered one of the most studied approaches to cancer treatment, with several heterocyclic compounds approved during the last 15 years as chemotherapeutic agents. Starting from the biological evaluation of an in-house collection of small molecules, indolinone was selected as the most promising scaffold. In this work, several functionalised indolinones were synthesised and their inhibitory potency and cytotoxic activity were assayed. The pharmacological profile of the most active compounds, supported by molecular modelling studies, revealed that the presence of an amino group increased the affinity towards the ATP-binding site of c-Src. At the same time, bulkier derivatizations seemed to improve the interactions within the enzymatic pocket. Overall, these data represent an early stage towards the optimisation of new, easy-to-be functionalised indolinones as potential c-Src inhibitors.

Keywords:

• c-Src
• indolinone
• Knoevenagel reaction
• molecular docking

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/[10.1080/14756366.2022.2133503)

Acknowledgements

We thank AIRC Foundation for Cancer Research in Italy (Fondazione AIRC per la Ricerca sul Cancro, AIRC): Grant IG-2017, project code 20762, PI Giovanni Maga iii) Grant IG-2020, project code 24448, PI Emmanuele Crespan; E.C. wishes to thank Cariplo Foundation, project 2019–1836.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by MIUR (PRIN 2017, project code 2017SA5837).