Design, synthesis and biological evaluation of a novel bioactive indane scaffold 2-(diphenylmethylene)c-2,3-dihydro-1H-inden-1-one with potential anticancer activity.

Over the past decades, designing of privileged structures has emerged as a useful approach to the discovery and optimisation of novel biologically active molecules, and many have been successfully exploited across and within different target families. Examples include indole, quinolone, isoquinoline, benzofuran and chromone, etc. In the current study, we focus on synthesising a novel hybrid scaffold constituting naturally occurring benzophenone (14) and indanone (22) ring systems, leading to a general structure of 2-(diphenylmethylene)-2,3-dihydro-1H-inden-1-one (23). It was hypothesised this new hybrid system would provide enhanced anti-cancer activity owing to the presence of the common features associated with the tubulin binding small molecule indanocine (10) and the estrogen receptor (ER) antagonist tamoxifen (24). Key hybrid molecules were successfully synthesised and characterised, and the in vitro cytotoxicity assays were performed against cancer cell lines: MCF7 (breast) and SKBR3 (breast), DU145 (prostate) and A549 (lung). The methyl-, chloro- and methoxy-, para-substituted benzophenone hybrids displayed the greatest degree of cytotoxicity and the E-configuration derivatives 45, 47 and 49 being significantly most potent. We further verified that the second benzyl moiety of this novel hybrid scaffold is fundamental to enhance the cytotoxicity, especially in the SKBR3 (HER2

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.