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.
References
Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jul 17, 1995·Journal of Immunological Methods·I VermesC Reutelingsperger
Jun 1, 1996·Cytometry·M van EngelandC P Reutelingsperger
Aug 24, 1999·Cancer Chemotherapy and Pharmacology·J P StevensonP J O'Dwyer
Jan 30, 2003·Acta histochemica·Dana KylarováVáclav Lichnovský
Apr 1, 2006·Journal of Chemotherapy·R T LimaM H Vasconcelos
Apr 5, 2007·Nature Protocols·Vanicha Vichai, Kanyawim Kirtikara
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
May 2, 2008·Investigational New Drugs·Priscila H GoncalvesPatricia M LoRusso
Jun 1, 1948·British Journal of Pharmacology and Chemotherapy·F HAWKING, W F ROSS
Dec 9, 2010·European Journal of Medicinal Chemistry·Maria-João R P QueirozM Helena Vasconcelos
Apr 19, 2011·European Journal of Medicinal Chemistry·Marta Perro NevesMaria de São José Nascimento
Sep 1, 2011·Journal of Natural Medicines·Hong-Bo ChenLaiqiang Huang
Sep 22, 2011·PloS One·Mamta D NaiduMichael J Waring
Nov 3, 2011·Biochemical Pharmacology·Andreia PalmeiraEmília Sousa
Dec 14, 2011·Carcinogenesis·Jeremy J JohnsonHasan Mukhtar
May 12, 2012·Journal of Biomedicine & Biotechnology·Hitomi KuroseYoshinori Otsuki
Jun 9, 2012·Journal of Proteomics·Wei-ming FuHsiang-fu Kung
Jun 29, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Syam MohanAsdren Zajmi
Jul 5, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hui-Fang Chang, Ling-Ling Yang
Mar 26, 2013·Current Medicinal Chemistry·A M PaivaE Sousa
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
Jul 13, 2019·Bioanalysis·João P do CarmoCarla Fernandes
Dec 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Raquel T LimaM Helena Vasconcelos
Jun 7, 2019·Pharmaceuticals·Viviana SilvaMadalena Pinto
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
Oct 30, 2020·Pharmaceuticals·Michele TonelliFabio Sparatore
Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Madalena M M PintoSara Cravo
Dec 8, 2019·Bioorganic Chemistry·Nahida Mokhtari Brikci-NigassaFlorence Mongin
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Fernando DurãesEmília Sousa