Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters
Authorized Users Only
2014
Authors
Savić, AleksandarMisirlić-Denčić, Sonja
Dulović, Marija
Mihajlović-Lalić, Ljiljana
Jovanović, Maja
Grgurić-Šipka, Sanja
Marković, Ivanka
Sabo, Tibor
Article (Published version)
Metadata
Show full item recordAbstract
This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds...' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved.
Keywords:
Amine ligands / Apoptosis / n-Butyl ester / Cyclohexyl analogues / Cytotoxic activity / Oxidative stressSource:
Bioorganic Chemistry, 2014, 54, 73-80Publisher:
- Academic Press Inc Elsevier Science, San Diego
Funding / projects:
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
DOI: 10.1016/j.bioorg.2014.04.006
ISSN: 0045-2068
PubMed: 24836201
WoS: 000338732900011
Scopus: 2-s2.0-84901287105
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Savić, Aleksandar AU - Misirlić-Denčić, Sonja AU - Dulović, Marija AU - Mihajlović-Lalić, Ljiljana AU - Jovanović, Maja AU - Grgurić-Šipka, Sanja AU - Marković, Ivanka AU - Sabo, Tibor PY - 2014 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1811 AB - This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved. PB - Academic Press Inc Elsevier Science, San Diego T2 - Bioorganic Chemistry T1 - Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters VL - 54 SP - 73 EP - 80 DO - 10.1016/j.bioorg.2014.04.006 ER -
@article{ author = "Savić, Aleksandar and Misirlić-Denčić, Sonja and Dulović, Marija and Mihajlović-Lalić, Ljiljana and Jovanović, Maja and Grgurić-Šipka, Sanja and Marković, Ivanka and Sabo, Tibor", year = "2014", abstract = "This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved.", publisher = "Academic Press Inc Elsevier Science, San Diego", journal = "Bioorganic Chemistry", title = "Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters", volume = "54", pages = "73-80", doi = "10.1016/j.bioorg.2014.04.006" }
Savić, A., Misirlić-Denčić, S., Dulović, M., Mihajlović-Lalić, L., Jovanović, M., Grgurić-Šipka, S., Marković, I.,& Sabo, T.. (2014). Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters. in Bioorganic Chemistry Academic Press Inc Elsevier Science, San Diego., 54, 73-80. https://doi.org/10.1016/j.bioorg.2014.04.006
Savić A, Misirlić-Denčić S, Dulović M, Mihajlović-Lalić L, Jovanović M, Grgurić-Šipka S, Marković I, Sabo T. Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters. in Bioorganic Chemistry. 2014;54:73-80. doi:10.1016/j.bioorg.2014.04.006 .
Savić, Aleksandar, Misirlić-Denčić, Sonja, Dulović, Marija, Mihajlović-Lalić, Ljiljana, Jovanović, Maja, Grgurić-Šipka, Sanja, Marković, Ivanka, Sabo, Tibor, "Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters" in Bioorganic Chemistry, 54 (2014):73-80, https://doi.org/10.1016/j.bioorg.2014.04.006 . .