Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines
2016
Аутори
Živković, MarijanaMatić, Ivana Z.
Rodić, Marko V.
Novaković, Irena
Sladić, Dušan
Krstić, Natalija
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
A series of new steroidal mono- and bis(thiosemicarbazones) (2a-e and 3a-e) and corresponding mono- and bis(1,3,4-thiadiazolines) (4a-e and 5a-e) was synthesized, characterized and evaluated for their anticancer activity. Detailed NMR analysis of the mono-and bis(thiosemicarbazones) revealed the presence of two stereoisomers (Z and E) with different configurations in the hydrazone moiety at the C-3 position, where the substituents on the C(3)]=N double bond in the main isomers adopted the E configuration. The configurations at C-3 and C-17 in thiadiazolines 4a-e and 5a-e were deduced by detailed NMR analysis as well as by the examination of Dreiding molecular models and X-ray analysis of 3-thiadiazoline 4a, which confirmed the structure and absolute configuration at C-3. The synthesized compounds were tested against six cancer cell lines (HeLa, K562, MDA-MB-361, MDA-MB-453, LS174 and A549), the normal human cell line MRC-5 and peripheral blood mononuclear cells (PBMC) isolated from hea...lthy donors. The best activity was exhibited by 3-thiosemicarbazones 2a, 2b, 2c and 2e and 3,17-bis(thiadiazolines) 5a and 5d. Examination of the mechanisms of cytotoxicity on cervical adenocarcinoma HeLa cells revealed the pro-apoptotic action of these compounds, which triggered both extrinsic and intrinsic apoptotic pathways. These compounds also showed the ability to decrease angiogenesis in vitro. In addition, 3,17-bis(thiadiazolines) 5a and 5d showed high selectivity in anticancer activity against all the examined malignant cell lines. Compound 5a displayed prominent anticancer potential. The tested compounds showed poor antimicrobial activity.
Извор:
RSC Advances, 2016, 6, 41, 34312-34333Издавач:
- Royal Soc Chemistry, Cambridge
Финансирање / пројекти:
- Интеракције природних производа, њихових деривата и комплексних једињења са протеинима и нуклеинским киселинама (RS-MESTD-Basic Research (BR or ON)-172055)
- Модификатори биолошког одговора у физиолошким и патолошким стањима (RS-MESTD-Basic Research (BR or ON)-175011)
DOI: 10.1039/c6ra01516f
ISSN: 2046-2069
WoS: 000374049700028
Scopus: 2-s2.0-84964664175
Институција/група
IHTMTY - JOUR AU - Živković, Marijana AU - Matić, Ivana Z. AU - Rodić, Marko V. AU - Novaković, Irena AU - Sladić, Dušan AU - Krstić, Natalija PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2028 AB - A series of new steroidal mono- and bis(thiosemicarbazones) (2a-e and 3a-e) and corresponding mono- and bis(1,3,4-thiadiazolines) (4a-e and 5a-e) was synthesized, characterized and evaluated for their anticancer activity. Detailed NMR analysis of the mono-and bis(thiosemicarbazones) revealed the presence of two stereoisomers (Z and E) with different configurations in the hydrazone moiety at the C-3 position, where the substituents on the C(3)]=N double bond in the main isomers adopted the E configuration. The configurations at C-3 and C-17 in thiadiazolines 4a-e and 5a-e were deduced by detailed NMR analysis as well as by the examination of Dreiding molecular models and X-ray analysis of 3-thiadiazoline 4a, which confirmed the structure and absolute configuration at C-3. The synthesized compounds were tested against six cancer cell lines (HeLa, K562, MDA-MB-361, MDA-MB-453, LS174 and A549), the normal human cell line MRC-5 and peripheral blood mononuclear cells (PBMC) isolated from healthy donors. The best activity was exhibited by 3-thiosemicarbazones 2a, 2b, 2c and 2e and 3,17-bis(thiadiazolines) 5a and 5d. Examination of the mechanisms of cytotoxicity on cervical adenocarcinoma HeLa cells revealed the pro-apoptotic action of these compounds, which triggered both extrinsic and intrinsic apoptotic pathways. These compounds also showed the ability to decrease angiogenesis in vitro. In addition, 3,17-bis(thiadiazolines) 5a and 5d showed high selectivity in anticancer activity against all the examined malignant cell lines. Compound 5a displayed prominent anticancer potential. The tested compounds showed poor antimicrobial activity. PB - Royal Soc Chemistry, Cambridge T2 - RSC Advances T1 - Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines VL - 6 IS - 41 SP - 34312 EP - 34333 DO - 10.1039/c6ra01516f ER -
@article{ author = "Živković, Marijana and Matić, Ivana Z. and Rodić, Marko V. and Novaković, Irena and Sladić, Dušan and Krstić, Natalija", year = "2016", abstract = "A series of new steroidal mono- and bis(thiosemicarbazones) (2a-e and 3a-e) and corresponding mono- and bis(1,3,4-thiadiazolines) (4a-e and 5a-e) was synthesized, characterized and evaluated for their anticancer activity. Detailed NMR analysis of the mono-and bis(thiosemicarbazones) revealed the presence of two stereoisomers (Z and E) with different configurations in the hydrazone moiety at the C-3 position, where the substituents on the C(3)]=N double bond in the main isomers adopted the E configuration. The configurations at C-3 and C-17 in thiadiazolines 4a-e and 5a-e were deduced by detailed NMR analysis as well as by the examination of Dreiding molecular models and X-ray analysis of 3-thiadiazoline 4a, which confirmed the structure and absolute configuration at C-3. The synthesized compounds were tested against six cancer cell lines (HeLa, K562, MDA-MB-361, MDA-MB-453, LS174 and A549), the normal human cell line MRC-5 and peripheral blood mononuclear cells (PBMC) isolated from healthy donors. The best activity was exhibited by 3-thiosemicarbazones 2a, 2b, 2c and 2e and 3,17-bis(thiadiazolines) 5a and 5d. Examination of the mechanisms of cytotoxicity on cervical adenocarcinoma HeLa cells revealed the pro-apoptotic action of these compounds, which triggered both extrinsic and intrinsic apoptotic pathways. These compounds also showed the ability to decrease angiogenesis in vitro. In addition, 3,17-bis(thiadiazolines) 5a and 5d showed high selectivity in anticancer activity against all the examined malignant cell lines. Compound 5a displayed prominent anticancer potential. The tested compounds showed poor antimicrobial activity.", publisher = "Royal Soc Chemistry, Cambridge", journal = "RSC Advances", title = "Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines", volume = "6", number = "41", pages = "34312-34333", doi = "10.1039/c6ra01516f" }
Živković, M., Matić, I. Z., Rodić, M. V., Novaković, I., Sladić, D.,& Krstić, N.. (2016). Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines. in RSC Advances Royal Soc Chemistry, Cambridge., 6(41), 34312-34333. https://doi.org/10.1039/c6ra01516f
Živković M, Matić IZ, Rodić MV, Novaković I, Sladić D, Krstić N. Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines. in RSC Advances. 2016;6(41):34312-34333. doi:10.1039/c6ra01516f .
Živković, Marijana, Matić, Ivana Z., Rodić, Marko V., Novaković, Irena, Sladić, Dušan, Krstić, Natalija, "Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines" in RSC Advances, 6, no. 41 (2016):34312-34333, https://doi.org/10.1039/c6ra01516f . .