Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis
João Barbosa,
Raquel T. Lima,
Diana Sousa,
Ana Sara Gomes,
Andreia Palmeira,
Hugo Seca,
Kantima Choosang,
Pannee Pakkong,
Hassan Bousbaa,
Madalena M. Pinto,
Emília Sousa,
M. Helena Vasconcelos,
Madalena Pedro
Affiliations
João Barbosa
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, IUCS—Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, Gandra 4585-116, Portugal
Raquel T. Lima
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal
Diana Sousa
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal
Ana Sara Gomes
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP—Faculty of Pharmacy of the University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
Andreia Palmeira
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP—Faculty of Pharmacy of the University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
Hugo Seca
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal
Applied Radiation and Isotopes Department, Faculty of Science, Kasetsart University, Jatujak, Bangkok 10930, Thailand
Hassan Bousbaa
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, IUCS—Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, Gandra 4585-116, Portugal
Madalena M. Pinto
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP—Faculty of Pharmacy of the University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
Emília Sousa
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP—Faculty of Pharmacy of the University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
M. Helena Vasconcelos
i3S—Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal
Madalena Pedro
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, IUCS—Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, Gandra 4585-116, Portugal
Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1·HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1·HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1·HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.
