Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes
Abstract
Cytoprotective compounds such as amifostine play an important role in chemo-and radiotherapy due to their ability to reduce the side effects of these treatments. Our work was initiated with the intention to design, synthesise and test a new class of heterocyclic compounds that would have an antioxidative profile with the potential to be further developed as cytoprotective agents. The design was based on the privileged tetrahydrobenzazepine scaffold found in many natural products with a wide range of biological properties. This structure was further functionalised with moieties known to possess antioxidative features such as tertiary amine and styrene double bond. A series of eight tetrahydrobenzazepine derivatives of isoquinoline, 3,4-dihydro-beta-carboline and pyridine were synthesised employing the Heck reaction as a key transformation. Some of the prepared compounds were tested for their in vitro effects on chromosome aberrations in peripheral human lymphocytes using the cytochalasi...n-B blocked micronucleus (MN) assay. Three tetrahydrobenzoazepine derivatives showed significant cytoprotective properties, comparable or even better to those of the radioprotective agent amifostine.
Keywords:
Cytoprotection / Heterocycles / Micronuclei / Synthesis / TetrahydrobenzazepineSource:
Archiv der Pharmazie, 2015, 348, 2, 100-112Publisher:
- Wiley-VCH Verlag GMBH, Weinheim
Funding / projects:
DOI: 10.1002/ardp.201400350
ISSN: 0365-6233
PubMed: 25664628
WoS: 000349628500003
Scopus: 2-s2.0-84922572924
Collections
Institution/Community
PharmacyTY - JOUR AU - Simić, Milena AU - Stanković, Miroslava AU - Mandić, Boris M. AU - Tešević, Vele AU - Savić, Vladimir PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2450 AB - Cytoprotective compounds such as amifostine play an important role in chemo-and radiotherapy due to their ability to reduce the side effects of these treatments. Our work was initiated with the intention to design, synthesise and test a new class of heterocyclic compounds that would have an antioxidative profile with the potential to be further developed as cytoprotective agents. The design was based on the privileged tetrahydrobenzazepine scaffold found in many natural products with a wide range of biological properties. This structure was further functionalised with moieties known to possess antioxidative features such as tertiary amine and styrene double bond. A series of eight tetrahydrobenzazepine derivatives of isoquinoline, 3,4-dihydro-beta-carboline and pyridine were synthesised employing the Heck reaction as a key transformation. Some of the prepared compounds were tested for their in vitro effects on chromosome aberrations in peripheral human lymphocytes using the cytochalasin-B blocked micronucleus (MN) assay. Three tetrahydrobenzoazepine derivatives showed significant cytoprotective properties, comparable or even better to those of the radioprotective agent amifostine. PB - Wiley-VCH Verlag GMBH, Weinheim T2 - Archiv der Pharmazie T1 - Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes VL - 348 IS - 2 SP - 100 EP - 112 DO - 10.1002/ardp.201400350 ER -
@article{ author = "Simić, Milena and Stanković, Miroslava and Mandić, Boris M. and Tešević, Vele and Savić, Vladimir", year = "2015", abstract = "Cytoprotective compounds such as amifostine play an important role in chemo-and radiotherapy due to their ability to reduce the side effects of these treatments. Our work was initiated with the intention to design, synthesise and test a new class of heterocyclic compounds that would have an antioxidative profile with the potential to be further developed as cytoprotective agents. The design was based on the privileged tetrahydrobenzazepine scaffold found in many natural products with a wide range of biological properties. This structure was further functionalised with moieties known to possess antioxidative features such as tertiary amine and styrene double bond. A series of eight tetrahydrobenzazepine derivatives of isoquinoline, 3,4-dihydro-beta-carboline and pyridine were synthesised employing the Heck reaction as a key transformation. Some of the prepared compounds were tested for their in vitro effects on chromosome aberrations in peripheral human lymphocytes using the cytochalasin-B blocked micronucleus (MN) assay. Three tetrahydrobenzoazepine derivatives showed significant cytoprotective properties, comparable or even better to those of the radioprotective agent amifostine.", publisher = "Wiley-VCH Verlag GMBH, Weinheim", journal = "Archiv der Pharmazie", title = "Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes", volume = "348", number = "2", pages = "100-112", doi = "10.1002/ardp.201400350" }
Simić, M., Stanković, M., Mandić, B. M., Tešević, V.,& Savić, V.. (2015). Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes. in Archiv der Pharmazie Wiley-VCH Verlag GMBH, Weinheim., 348(2), 100-112. https://doi.org/10.1002/ardp.201400350
Simić M, Stanković M, Mandić BM, Tešević V, Savić V. Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes. in Archiv der Pharmazie. 2015;348(2):100-112. doi:10.1002/ardp.201400350 .
Simić, Milena, Stanković, Miroslava, Mandić, Boris M., Tešević, Vele, Savić, Vladimir, "Synthesis of Novel Tetrahydrobenzazepine Derivatives and Their Cytoprotective Effect on Human Lymphocytes" in Archiv der Pharmazie, 348, no. 2 (2015):100-112, https://doi.org/10.1002/ardp.201400350 . .