Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D
Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-09-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/13/9/5784 |
| _version_ | 1811184709761236992 |
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| author | Brett D. Schwartz Mark J. Coster Tina S. Skinner-Adams Katherine T. Andrews Jonathan M. White Rohan A. Davis |
| author_facet | Brett D. Schwartz Mark J. Coster Tina S. Skinner-Adams Katherine T. Andrews Jonathan M. White Rohan A. Davis |
| author_sort | Brett D. Schwartz |
| collection | DOAJ |
| description | Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells. |
| first_indexed | 2024-04-11T13:17:03Z |
| format | Article |
| id | doaj.art-623c45ec2ba348dcb643745991d2732a |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:17:03Z |
| publishDate | 2015-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-623c45ec2ba348dcb643745991d2732a2022-12-22T04:22:22ZengMDPI AGMarine Drugs1660-33972015-09-011395784579510.3390/md13095784md13095784Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–DBrett D. Schwartz0Mark J. Coster1Tina S. Skinner-Adams2Katherine T. Andrews3Jonathan M. White4Rohan A. Davis5Eskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, AustraliaEskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, AustraliaEskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, AustraliaEskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, AustraliaSchool of Chemistry and Bio21 Institute, University of Melbourne, Parkville, Vic 3052, AustraliaEskitis Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, AustraliaSix regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells.http://www.mdpi.com/1660-3397/13/9/5784synthesisthiaplakortoneregioisomertricyclicnatural product scaffoldX-raycrystalPlasmodium falciparumantiplasmodialcytotoxicity |
| spellingShingle | Brett D. Schwartz Mark J. Coster Tina S. Skinner-Adams Katherine T. Andrews Jonathan M. White Rohan A. Davis Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D Marine Drugs synthesis thiaplakortone regioisomer tricyclic natural product scaffold X-ray crystal Plasmodium falciparum antiplasmodial cytotoxicity |
| title | Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D |
| title_full | Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D |
| title_fullStr | Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D |
| title_full_unstemmed | Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D |
| title_short | Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D |
| title_sort | synthesis and antiplasmodial evaluation of analogues based on the tricyclic core of thiaplakortones a d |
| topic | synthesis thiaplakortone regioisomer tricyclic natural product scaffold X-ray crystal Plasmodium falciparum antiplasmodial cytotoxicity |
| url | http://www.mdpi.com/1660-3397/13/9/5784 |
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