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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Barbosa, J (Author) Other; Lima, RT (Author) Other; Sousa, D (Author) Other; Gomes, AS (Author) Other; Palmeira, A (Author) FFUP; Seca, H (Author) Other; Choosang, K (Author) Other; Pakkong, P (Author) Other; Bousbaa, H (Author) Other; Pinto, MM (Author) Other; Emilia Sousa (Author) FFUP; Helena Vasconcelos, MH (Author) FFUP; Pedro, M (Author) Other

Journal

Title: Molecules

Vol. 21 No. 7

Final page: 81

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 18 Citations

Other information

Authenticus ID: P-00K-6F0

DOI: 10.3390/molecules21010081

Abstract (EN): 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 TXA1HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15