New chalcone derivatives with suitable drug-like lipophilicity targeting mitosis

Abstract

Chalcones are natural flavonoid precursors that have been reported for their wide range of biological activities, namely antitumor [1-2]. In addition, the presence of an α,β-unsaturated ketone moiety makes these compounds a valuable chemical substrate for the synthesis of bioactive derivatives, such as pyrazoles [3]. Our research group has reported two synthetic chalcone derivatives with antimitotic effect [4-5]. Hence, in continuation of our efforts to obtain new chalcone derivatives with improved antitumor and antimitotic activity, a small library of chalcone derivatives, including pyrazole and α,b-epoxide, was synthesized and evaluated for their cell growth inhibitory activity in three human tumor cell lines. Additionally, their lipophilicity using liposomes as a biomimetic membrane model was determined. From this work, nine chalcones showing suitable drug-like lipophilicity with antimitotic effect were identified. Moreover, one of the compounds was able to enhance chemosensitivity of tumor cells to paclitaxel in NCI-H460 cells. Acknowledgments This research was partially supported by the Strategic Funding UID/Multi/04423/2019 and under the project PTDC/SAU-PUB/28736/2017 (reference POCI-01-0145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF and by FCT through national funds. This work was also supported through funds provided by CESPU, Crl under the project ComeTarget_CESPU_2017. Ana Henriques, Joana Moreira and José Soares acknowledge for their FCT grants (SFRH/BD/111365/2015 and SFRH/BD/135852/2018, and SFRH/BD/98105/2013, respectively).