Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity
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2002
Authors
Šolaja, BogdanTerzić, Nataša
Pocsfalvi, Gabriella
Gerena, L.
Tinant, Bernard
Opsenica, Dejan
Milhous, Wilbur K.
Article (Published version)
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Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 μM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further tra...nsformed into corresponding acids and amides.
Source:
Journal of Medicinal Chemistry, 2002, 45, 16, 3331-3336Publisher:
- American Chemical Society (ACS)
DOI: 10.1021/jm020891g
ISSN: 0022-2623
PubMed: 12139444
WoS: 000177142800002
Scopus: 2-s2.0-0036682037
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IHTMTY - JOUR AU - Šolaja, Bogdan AU - Terzić, Nataša AU - Pocsfalvi, Gabriella AU - Gerena, L. AU - Tinant, Bernard AU - Opsenica, Dejan AU - Milhous, Wilbur K. PY - 2002 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/91 AB - Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 μM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides. PB - American Chemical Society (ACS) T2 - Journal of Medicinal Chemistry T1 - Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity VL - 45 IS - 16 SP - 3331 EP - 3336 DO - 10.1021/jm020891g ER -
@article{ author = "Šolaja, Bogdan and Terzić, Nataša and Pocsfalvi, Gabriella and Gerena, L. and Tinant, Bernard and Opsenica, Dejan and Milhous, Wilbur K.", year = "2002", abstract = "Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 μM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.", publisher = "American Chemical Society (ACS)", journal = "Journal of Medicinal Chemistry", title = "Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity", volume = "45", number = "16", pages = "3331-3336", doi = "10.1021/jm020891g" }
Šolaja, B., Terzić, N., Pocsfalvi, G., Gerena, L., Tinant, B., Opsenica, D.,& Milhous, W. K.. (2002). Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity. in Journal of Medicinal Chemistry American Chemical Society (ACS)., 45(16), 3331-3336. https://doi.org/10.1021/jm020891g
Šolaja B, Terzić N, Pocsfalvi G, Gerena L, Tinant B, Opsenica D, Milhous WK. Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity. in Journal of Medicinal Chemistry. 2002;45(16):3331-3336. doi:10.1021/jm020891g .
Šolaja, Bogdan, Terzić, Nataša, Pocsfalvi, Gabriella, Gerena, L., Tinant, Bernard, Opsenica, Dejan, Milhous, Wilbur K., "Mixed steroidal 1,2,4,5-tetraoxanes: Antimalarial and antimycobacterial activity" in Journal of Medicinal Chemistry, 45, no. 16 (2002):3331-3336, https://doi.org/10.1021/jm020891g . .