N⁴-Phenyl-substituted 2-acetylpyridine thiosemicarbazones: cytotoxicity against human tumor cells, structure-activity relationship studies and investigation on the mechanism of action

Bioorganic & Medicinal Chemistry
Marcella A SoaresHeloisa Beraldo

Abstract

N(4)-Phenyl 2-acetylpyridine thiosemicarbazone (H2Ac4Ph; N-(phenyl)-2-(1-(pyridin-2-yl)ethylidene)hydrazinecarbothioamide) and its N(4)-ortho-, -meta- and -para-fluorophenyl (H2Ac4oFPh, H2Ac4mFPh, H2Ac4pFPh), N(4)-ortho-, -meta- and -para-chlorophenyl (H2Ac4oClPh, H2Ac4mClPh, H2Ac4pClPh), N(4)-ortho-, -meta- and -para-iodophenyl (H2Ac4oIPh, H2Ac4mIPh, H2Ac4pIPh) and N(4)-ortho-, -meta- and -para-nitrophenyl (H2Ac4oNO(2)Ph, H2Ac4mNO(2)Ph, H2Ac4pNO(2)Ph) derivatives were assayed for their cytotoxicity against human malignant breast (MCF-7) and glioma (T98G and U87) cells. The compounds were highly cytotoxic against the three cell lineages (IC(50): MCF-7, 52-0.16 nM; T98G, 140-1.0 nM; U87, 160-1.4 nM). All tested thiosemicarbazones were more cytotoxic than etoposide and did not present any haemolytic activity at up to 10(-5)M. The compounds were able to induce programmed cell death. H2Ac4pClPh partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization.

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Citations

Jan 25, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Josane A LessaHeloisa Beraldo
Jun 12, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Karina S O FerrazHeloisa Beraldo
Oct 30, 2012·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Catherine LambertMilena Salerno
Oct 17, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Débora C ReisHeloisa Beraldo
Sep 27, 2016·Micron : the International Research and Review Journal for Microscopy·Sinara Mônica Vitalino de AlmeidaLuiz Bezerra de Carvalho Júnior
Dec 24, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Alexandre A OliveiraHeloisa Beraldo
Sep 22, 2017·Acta Crystallographica. Section E, Crystallographic Communications·Sayed RiyadhMusa A Said
Aug 2, 2017·Expert Opinion on Drug Discovery·Hui-Yun HwangHo Jeong Kwon
Jan 7, 2019·Molecular Diversity·Fatih SonmezMustafa Kucukislamoglu
Dec 26, 2018·European Journal of Medicinal Chemistry·Guilherme Felipe Dos Santos FernandesJean Leandro Dos Santos
Jun 1, 2021·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Susobhan MahantyKrishnan Rathinasamy

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