title: Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.
abstract: 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.
authors.affiliation: Faculty of Medicinal Science, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Milorad Z
authors.initials: MZ
authors.lastname: Milošev
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Jakovljević
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Milan D
authors.initials: MD
authors.lastname: Joksović
authors.affiliation: Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stanojković
authors.affiliation: Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: Ivana Z
authors.initials: IZ
authors.lastname: Matić
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Belgrade, Serbia.
authors.forename: Milka
authors.initials: M
authors.lastname: Perović
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Tešić
authors.affiliation: Institute for Biological Research "Siniša Stanković", Department of Neurobiology, University of Belgrade, Belgrade, Serbia.
authors.forename: Selma
authors.initials: S
authors.lastname: Kanazir
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Mladenović
authors.affiliation: Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Marko V
authors.initials: MV
authors.lastname: Rodić
authors.affiliation: Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Vukadin M
authors.initials: VM
authors.lastname: Leovac
authors.affiliation: Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Snežana
authors.initials: S
authors.lastname: Trifunović
authors.affiliation: Faculty of Science, Department of Chemistry, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Violeta
authors.initials: V
authors.lastname: Marković
mesh_terms: D000218:Adamantane / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008352:Mannich Bases / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008352:Mannich Bases; D013871:Thiones; D014230:Triazoles; C045575:1,2,4-triazole; D000218:Adamantane
keywords: Mannich bases; adamantane; anticancer activity; molecular modeling; triazoles