Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
João BarbosaMadalena Pedro

Abstract

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.

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Citations

Oct 14, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Raquel T LimaM Helena Vasconcelos
Jan 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ye' Zaw PhyoCarla Fernandes
May 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agostinho LemosMaria Emília Sousa
Dec 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Raquel T LimaM Helena Vasconcelos
Jun 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Penghui WangLu Zhou
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Diana I S P ResendeMadalena M M Pinto
Dec 8, 2020·Expert Opinion on Drug Metabolism & Toxicology·Vera SilvaRenata Silva
Jun 25, 2019·International Journal of Biological Macromolecules·Carlos FloresPaula Tamagnini
Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Madalena M M PintoSara Cravo
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fernando DurãesEmília Sousa

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Methods Mentioned

BETA
xenograft
fluorescence microscopy
flow cytometry
Assay

Software Mentioned

Nikon ACT - 1
WinFirst
FlowJo
GraphPad Prism

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