Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies
2017
Authors:
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
Document Type:
Article (Published version)
,
© 2016 John Wiley & Sons A/S.
Metadata
Show full item recordAbstract:
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.
Keywords:
Mannich bases; Adamantane; anticancer activity; molecular modeling; triazolesFunding / projects:
- Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes (RS-MESTD-Basic Research (BR or ON)-172016)
- Biological response modifiers in physiological and pathological conditions (RS-MESTD-Basic Research (BR or ON)-175011)
- Brain plasticity in aging: effect of dietary restriction and anesthesia (RS-MESTD-Basic Research (BR or ON)-173056)
- Simultaneous Bioremediation and Soilification of Degraded Areas to Preserve Natural Resources of Biologically Active Substances, and Development and Production of Biomaterials and Dietetic Products (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-43004)
In:
- 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