Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity
Fernando Durães,
Patrícia M. A. Silva,
Pedro Novais,
Isabel Amorim,
Luís Gales,
Cátia I. C. Esteves,
Samuel Guieu,
Hassan Bousbaa,
Madalena Pinto,
Emília Sousa
Affiliations
Fernando Durães
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Patrícia M. A. Silva
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
Pedro Novais
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
Isabel Amorim
GreenUPorto (Sustainable Agrifood Production) Research Center, Faculty of Sciences, University of Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
Luís Gales
Department of Molecular Biology, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Cátia I. C. Esteves
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Samuel Guieu
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Hassan Bousbaa
CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
Madalena Pinto
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Emília Sousa
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
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 GI50 values below 10 µM 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.
