Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity


Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline-chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI(50) values below 10 mu M for the three tested cell lines, and structure-activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.



subject category

Biochemistry & Molecular Biology; Chemistry, Multidisciplinary


Duraes, F; Silva, PMA; Novais, P; Amorim, I; Gales, L; Esteves, CIC; Guieu, S; Bousbaa, H; Pinto, M; Sousa, E

our authors


This research was partially supported by the Strategic Funding UIDB/04423/2020, UIDP/0 4423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) 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. Fernando Duraes acknowledges his FCT grant (SFRH/BD/144681/2019). Hassan Bousbaa acknowledges funding from CESPU (IMPLDEBRIS-PL-3RL-IINFACTS-2019). This research was funded by Fundacao para a Ciencia e a Tecnologia (FCT) through research units UIDB/50006/2020, UID/CTM/50011/2019, UIDB/50011/2020 & UIDP/50011/2020 and by the European Union (FEDER program) through project CENTRO-01-0145-FEDER-000003.

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