Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials
Само за регистроване кориснике
2008
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis ...of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.
Извор:
Journal of Medicinal Chemistry, 2008, 51, 7, 2261-2266Издавач:
- Amer Chemical Soc, Washington
Финансирање / пројекти:
- Пероксидни антималарици и њихове химере са хинолинима: синтеза и биолошка активност (RS-MESTD-MPN2006-2010-142022)
DOI: 10.1021/jm701417a
ISSN: 0022-2623
PubMed: 18330976
WoS: 000254709100031
Scopus: 2-s2.0-41849117634
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Opsenica, Igor AU - Opsenica, Dejan M. AU - Smith, Kirsten S. AU - Milhous, Wilbur K. AU - Šolaja, Bogdan A. PY - 2008 UR - https://cherry.chem.bg.ac.rs/handle/123456789/926 AB - The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies. PB - Amer Chemical Soc, Washington T2 - Journal of Medicinal Chemistry T1 - Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials VL - 51 IS - 7 SP - 2261 EP - 2266 DO - 10.1021/jm701417a ER -
@article{ author = "Opsenica, Igor and Opsenica, Dejan M. and Smith, Kirsten S. and Milhous, Wilbur K. and Šolaja, Bogdan A.", year = "2008", abstract = "The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.", publisher = "Amer Chemical Soc, Washington", journal = "Journal of Medicinal Chemistry", title = "Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials", volume = "51", number = "7", pages = "2261-2266", doi = "10.1021/jm701417a" }
Opsenica, I., Opsenica, D. M., Smith, K. S., Milhous, W. K.,& Šolaja, B. A.. (2008). Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials. in Journal of Medicinal Chemistry Amer Chemical Soc, Washington., 51(7), 2261-2266. https://doi.org/10.1021/jm701417a
Opsenica I, Opsenica DM, Smith KS, Milhous WK, Šolaja BA. Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials. in Journal of Medicinal Chemistry. 2008;51(7):2261-2266. doi:10.1021/jm701417a .
Opsenica, Igor, Opsenica, Dejan M., Smith, Kirsten S., Milhous, Wilbur K., Šolaja, Bogdan A., "Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane Antimalarials" in Journal of Medicinal Chemistry, 51, no. 7 (2008):2261-2266, https://doi.org/10.1021/jm701417a . .