Hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl- and vinylketo-benzofuroxans developed as anti-trypanosomatid agents, against Trypanosoma cruzi and Leishmania spp., have showed low micromolar IC(50) values. The synthetic route to access to these derivatives was an efficient Wittig reaction performed in mild conditions with polymer-supported triphenylphosphine (PS-TPP). Additionally, the more ..
Target
| Sequence: RecName: Full=Cruzipain; AltName: Full=Cruzaine; AltName: Full=Major cysteine proteinase; Flags: Precursor Description ..   Protein Family: Peptidase_C1A Comment .. Related Protein 3D Structures |
Tested Compounds:
Description:
Title: Anti-trypanosomatid benzofuroxans and deoxygenated analogues: synthesis using polymer-supported triphenylphosphine, biological evaluation and mechanism of action studies.
Abstract: Hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl- and vinylketo-benzofuroxans developed as anti-trypanosomatid agents, against Trypanosoma cruzi and Leishmania spp., have showed low micromolar IC(50) values. The synthetic route to access to these derivatives was an efficient Wittig reaction performed in mild conditions with polymer-supported triphenylphosphine (PS-TPP). Additionally, the benzofurozan analogues, deoxygenated benzofuroxans, were prepared using PS-TPP as reductive reagent in excellent yields. The trypanosomicidal and leishmanocidal activities of the benzofuroxan derivatives were measured and also some aspects of their mechanism of action studied. In this sense, inhibition of mitochondrial dehydrogenases activities, production of intra-parasite free radicals and cruzipain inhibition were studied as biological target for the anti-trypanosomatid identified compounds. The trypanosomicidal activity could be the result of both the parasite-mitochondrion function interference and production of oxidative stress into the parasite.
(PMID: 19837489)
Abstract: Hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl- and vinylketo-benzofuroxans developed as anti-trypanosomatid agents, against Trypanosoma cruzi and Leishmania spp., have showed low micromolar IC(50) values. The synthetic route to access to these derivatives was an efficient Wittig reaction performed in mild conditions with polymer-supported triphenylphosphine (PS-TPP). Additionally, the benzofurozan analogues, deoxygenated benzofuroxans, were prepared using PS-TPP as reductive reagent in excellent yields. The trypanosomicidal and leishmanocidal activities of the benzofuroxan derivatives were measured and also some aspects of their mechanism of action studied. In this sense, inhibition of mitochondrial dehydrogenases activities, production of intra-parasite free radicals and cruzipain inhibition were studied as biological target for the anti-trypanosomatid identified compounds. The trypanosomicidal activity could be the result of both the parasite-mitochondrion function interference and production of oxidative stress into the parasite.
(PMID: 19837489)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 10452
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 10452
ChEMBL target type: Target is a single protein chain
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Inhibition activity comment | Inhibition activity comment | String | |||
| 2 | Inhibition standard flag | Inhibition standard flag |  | Integer | ||
| 3 | Inhibition qualifier | Inhibition qualifier | String | |||
| 4 | Inhibition published value | Inhibition published value | | Float | % | |
| 5 | Inhibition standard value | Inhibition standard value | | Float | % |
Data Table (Concise)
PageFrom: