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Promising caspase modulators with flavonoid scaffold
1 , 2 , 2 , 3 , 2 , * 3, 4
1  Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal
2  Laboratório de Microbiologia, Departamento de Ciências Biológicas and UCIBIO/REQUIMTE, Faculdade de Farmácia, Universidade do Porto, Portugal.
3  Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
4  Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n 4450-208 Matosinhos, Portugal

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

Flavonoids represent an interesting class of naturally occurring compounds that have been attracting attention of the scientific community because of their wide range of biological properties, being the antitumor activity one of the most studied. The antitumor activity of flavonoids is associated with, at least in part, their ability to induce apoptosis by affecting the expression or activity of a wide variety of molecules involved in apoptosis pathways, namely the caspase family proteins [1]. As a result of the search for new bioactive compounds with antitumor activity by our research group, two flavonoids have been identified as procaspase-7 activators [2]. Inspired by the potential of these flavonoids as caspase modulators, we have synthesized several analogues using natural flavonoids, as the starting material. The synthetic approach was based on the reaction with alkyl halides in alkaline medium under microwave irradiation. The structure elucidation of synthesized compounds was established on the basis of NMR techniques (1H NMR, 13C NMR, HSQC and HMBC). Some of the synthesized compounds were evaluated for their ability to modulate procaspases-3 and 7 activity using yeast cell based assays [2]. Molecular docking studies with procaspases-3, 6 and 7 were also performed.


[1] Ravishankar, D., Rajora, A. K., Greco, F., Osborn, H. M. (2013), Flavonoids as Prospective Compounds for Anti-cancer Therapy, The International Journal of Biochemistry & Cell Biology, 45(12), 2821-2831.

[2] Pereira, C., Lopes-Rodrigues, V., Coutinho, I., Neves, M. P., Lima, R. T., Pinto, M., Saraiva, L. (2014), Potential Small-molecule Activators of Caspase-7 Identified Using Yeast-based Caspase-3 and-7 Screening Assays, European Journal of Pharmaceutical Sciences, 54, 8-16.


This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT – Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020 and the projects TDC/DTP-FTO/1981/2014 and REQUIMTE-Pest-C/EQB/LA0006/2013.

Keywords: Cancer, Caspase Activators, Flavonoids