Protoflavone – spirooxindole hybrids exhibit promising, increased antitumor activity

Protoflavones are rare natural flavonoids with a non-aromatic B ring, typically found in fern species. Several of these compounds show promising antitumor effects in vitro on various cell lines and in vivo. These protoflavones induce apoptosis and are capable to inhibit the ATR-mediated activation of checkpoint kinase 1, a crucial step in DNA damage response [1].

Spiropyrazoline oxindoles are found to induce apoptosis and upregulate p53 steady-state levels [2].

In this study we aimed to combine the aforementioned two compound groups with different antitumor mechanisms, gaining new hybrids with increased antitumor activity.

Utilizing modified sidechains and copper(I) catalysed azide-alkyne cycloaddition reactions we synthesized 8 new hybrid compounds so far.

The antitumor tests are in progress on multiple cell lines. Preliminary results look promising, as for example one of tested hybrid compounds showed 87.9±1.1% inhibition on MDA-MB-231 cell line at 5uM concentration, significantly higher than that of the fragments.

Acknowledgement: Supported by the ÚNKP-20-3 - New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund and FUNDAÇÃO PARA ciência e tecnologia (FCT) through COOPERAÇÃO CIENTÍFICA E TECNOLÓGICA FCT/NKFIH 2019/2020, UIDB/04138/2020 (IMED.ULISBOA), and PhD fellowships SFRH/BD/137544/2018 and SFRH/BD/117931/2016.

Publication History

Article published online:
13 December 2021

• References

• 1 Latif AD. et al. Antioxidants 2020; 9 (06) 519
• 2 Nunes RC. et al. European Journal of Medicinal Chemistry 2017; 139: 168-179