Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies
Само за регистроване кориснике
2017
Аутори
Milošev, Milorad Z.Jakovljević, Katarina
Joksović, Milan D.
Stanojković, Tatjana
Matić, Ivana Z.
Perović, Milka
Tešić, Vesna
Kanazir, Selma
Mladenović, Milan
Rodić, Marko
Leovac, Vukadin M.
Trifunović, Snežana S.
Marković, Violeta
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-th ione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b,5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA. hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular... docking/molecular dynamics approach.
Кључне речи:
adamantane / anticancer activity / Mannich bases / molecular modeling / triazolesИзвор:
Chemical Biology and Drug Design, 2017, 89, 6, 943-952Издавач:
- Wiley, Hoboken
Финансирање / пројекти:
- Синтеза, моделовање, физичко-хемијске и биолошке особине органских једињења и одговарајућих комплекса метала (RS-172016)
- Модификатори биолошког одговора у физиолошким и патолошким стањима (RS-175011)
- Симултана биоремедијација и соилификација деградираних простора, за очување природних ресурса биолошки активних супстанци и развој и производњу биоматеријала и дијететских производа (RS-43004)
- Пластичност мозга током старења: утицај дијеталне рестрикције и анестезије (RS-173056)
Напомена:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3221
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3222
DOI: 10.1111/cbdd.12920
ISSN: 1747-0277
PubMed: 27933733
WoS: 000405100700012
Scopus: 2-s2.0-85019213707
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Milošev, Milorad Z. AU - Jakovljević, Katarina AU - Joksović, Milan D. AU - Stanojković, Tatjana AU - Matić, Ivana Z. AU - Perović, Milka AU - Tešić, Vesna AU - Kanazir, Selma AU - Mladenović, Milan AU - Rodić, Marko AU - Leovac, Vukadin M. AU - Trifunović, Snežana S. AU - Marković, Violeta PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2482 AB - A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-th ione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b,5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA. hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach. PB - Wiley, Hoboken T2 - Chemical Biology and Drug Design T1 - Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies VL - 89 IS - 6 SP - 943 EP - 952 DO - 10.1111/cbdd.12920 ER -
@article{ author = "Milošev, Milorad Z. and Jakovljević, Katarina and Joksović, Milan D. and Stanojković, Tatjana and Matić, Ivana Z. and Perović, Milka and Tešić, Vesna and Kanazir, Selma and Mladenović, Milan and Rodić, Marko and Leovac, Vukadin M. and Trifunović, Snežana S. and Marković, Violeta", year = "2017", abstract = "A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-th ione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells. The effects of compounds 5b,5e, and 5j on the cell cycle were investigated by flow cytometric analysis. It was found that these compounds cause the accumulation of cells in the subG1 and G1 phases of the cell cycle and induce caspase-dependent apoptosis, while the anti-angiogenic effects of 5b, 5e, and 5j have been confirmed in EA. hy926 cells using a tube formation assay. Further, the interaction of Bax protein with compound 5b was investigated by means of molecular modeling, applying the combined molecular docking/molecular dynamics approach.", publisher = "Wiley, Hoboken", journal = "Chemical Biology and Drug Design", title = "Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies", volume = "89", number = "6", pages = "943-952", doi = "10.1111/cbdd.12920" }
Milošev, M. Z., Jakovljević, K., Joksović, M. D., Stanojković, T., Matić, I. Z., Perović, M., Tešić, V., Kanazir, S., Mladenović, M., Rodić, M., Leovac, V. M., Trifunović, S. S.,& Marković, V.. (2017). Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies. in Chemical Biology and Drug Design Wiley, Hoboken., 89(6), 943-952. https://doi.org/10.1111/cbdd.12920
Milošev MZ, Jakovljević K, Joksović MD, Stanojković T, Matić IZ, Perović M, Tešić V, Kanazir S, Mladenović M, Rodić M, Leovac VM, Trifunović SS, Marković V. Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies. in Chemical Biology and Drug Design. 2017;89(6):943-952. doi:10.1111/cbdd.12920 .
Milošev, Milorad Z., Jakovljević, Katarina, Joksović, Milan D., Stanojković, Tatjana, Matić, Ivana Z., Perović, Milka, Tešić, Vesna, Kanazir, Selma, Mladenović, Milan, Rodić, Marko, Leovac, Vukadin M., Trifunović, Snežana S., Marković, Violeta, "Mannich bases of 1,2,4-triazole--3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies" in Chemical Biology and Drug Design, 89, no. 6 (2017):943-952, https://doi.org/10.1111/cbdd.12920 . .