Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro
Аутори
Živković, Marijana B.Matić, Ivana Z.
Rodić, Marko
Novaković, Irena T.
Krivokuća, Ana M.
Sladić, Dušan
Krstić, Natalija M.
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (5)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC5...0 values from 8.5 mu M to 14.9 mu M), eight on HeLa cells (IC50 values ranging from 8.9 mu M to 15.1 mu M) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC50 values from 12.7 mu M to 25.6 mu M) than cisplatin (21.5 mu M) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activity.
Кључне речи:
1,3-Thiazolidin-4-ones / Anti-angiogenic effect / Apoptosis / Cytotoxic activity / Steroidal thiosemicarbazonesИзвор:
Journal of Steroid Biochemistry and Molecular Biology, 2017, 174, 72-85Издавач:
- Pergamon-Elsevier Science Ltd, Oxford
Финансирање / пројекти:
- Интеракције природних производа, њихових деривата и комплексних једињења са протеинима и нуклеинским киселинама (RS-172055)
- Модификатори биолошког одговора у физиолошким и патолошким стањима (RS-175011)
Напомена:
- This is the peer-reviewed version of the following article: Živković, M. B.; Matić, I. Z.; Rodić, M. V.; Novaković, I. T.; Krivokuća, A. M.; Sladić, D. M.; Krstić, N. M. Anticancer Potential of New Steroidal Thiazolidin-4-One Derivatives. Mechanisms of Cytotoxic Action and Effects on Angiogenesis in Vitro. Journal of Steroid Biochemistry and Molecular Biology 2017, 174, 72–85. https://doi.org/10.1016/j.jsbmb.2017.07.031
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3192
DOI: 10.1016/j.jsbmb.2017.07.031
ISSN: 0960-0760
WoS: 000414880600010
Scopus: 2-s2.0-85028028880
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Živković, Marijana B. AU - Matić, Ivana Z. AU - Rodić, Marko AU - Novaković, Irena T. AU - Krivokuća, Ana M. AU - Sladić, Dušan AU - Krstić, Natalija M. PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3191 AB - The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (5)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC50 values from 8.5 mu M to 14.9 mu M), eight on HeLa cells (IC50 values ranging from 8.9 mu M to 15.1 mu M) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC50 values from 12.7 mu M to 25.6 mu M) than cisplatin (21.5 mu M) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activity. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Journal of Steroid Biochemistry and Molecular Biology T1 - Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro VL - 174 SP - 72 EP - 85 DO - 10.1016/j.jsbmb.2017.07.031 ER -
@article{ author = "Živković, Marijana B. and Matić, Ivana Z. and Rodić, Marko and Novaković, Irena T. and Krivokuća, Ana M. and Sladić, Dušan and Krstić, Natalija M.", year = "2017", abstract = "The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (5)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC50 values from 8.5 mu M to 14.9 mu M), eight on HeLa cells (IC50 values ranging from 8.9 mu M to 15.1 mu M) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC50 values from 12.7 mu M to 25.6 mu M) than cisplatin (21.5 mu M) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activity.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Journal of Steroid Biochemistry and Molecular Biology", title = "Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro", volume = "174", pages = "72-85", doi = "10.1016/j.jsbmb.2017.07.031" }
Živković, M. B., Matić, I. Z., Rodić, M., Novaković, I. T., Krivokuća, A. M., Sladić, D.,& Krstić, N. M.. (2017). Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro. in Journal of Steroid Biochemistry and Molecular Biology Pergamon-Elsevier Science Ltd, Oxford., 174, 72-85. https://doi.org/10.1016/j.jsbmb.2017.07.031
Živković MB, Matić IZ, Rodić M, Novaković IT, Krivokuća AM, Sladić D, Krstić NM. Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro. in Journal of Steroid Biochemistry and Molecular Biology. 2017;174:72-85. doi:10.1016/j.jsbmb.2017.07.031 .
Živković, Marijana B., Matić, Ivana Z., Rodić, Marko, Novaković, Irena T., Krivokuća, Ana M., Sladić, Dušan, Krstić, Natalija M., "Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro" in Journal of Steroid Biochemistry and Molecular Biology, 174 (2017):72-85, https://doi.org/10.1016/j.jsbmb.2017.07.031 . .