Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies
2017
Аутори:
Milošev, Milorad ZJakovljević, Katarina
Joksović, Milan D
Stanojković, Tatjana
Matić, Ivana Z
Perović, Milka
Tešić, Vesna
Kanazir, Selma
Mladenović, Milan
Rodić, Marko V
Leovac, Vukadin M
Trifunović, Snežana
Marković, Violeta
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2016 John Wiley & Sons A/S.
Метаподаци
Приказ свих података о документуАпстракт:
A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione 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:
Mannich bases; Adamantane; anticancer activity; molecular modeling; triazolesФинансирање / пројекти:
- Синтеза, моделовање, физичко-хемијске и биолошке особине органских једињења и одговарајућих комплекса метала (RS-MESTD-Basic Research (BR or ON)-172016)
- Модификатори биолошког одговора у физиолошким и патолошким стањима (RS-MESTD-Basic Research (BR or ON)-175011)
- Пластичност мозга током старења: утицај дијеталне рестрикције и анестезије (RS-MESTD-Basic Research (BR or ON)-173056)
- Симултана биоремедијација и соилификација деградираних простора, за очување природних ресурса биолошки активних супстанци и развој и производњу биоматеријала и дијететских производа (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-43004)
У:
- Chemical Biology & Drug Design (2017), 89(6): 943-952
DOI: 10.1111/cbdd.12920
ISSN: 1747-0277
PubMed: 27933733
WoS: 000405100700012
Scopus: 2-s2.0-85019213707
URI
http://doi.wiley.com/10.1111/cbdd.12920http://www.ncbi.nlm.nih.gov/pubmed/27933733
https://radar.ibiss.bg.ac.rs/handle/123456789/2753