Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures
A three-dimensional QSAR pharmacophore model for antimalarial activity of steroidal 1,2,4,5-tetraoxanes was developed from a set of 17 substituted antimalarial derivatives out of 27 analogues that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plas...
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| Format: | Article |
| Language: | English |
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Serbian Chemical Society
2005-03-01
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| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | http://www.shd.org.yu/HtDocs/SHD/vol70/No3/JSCS_V70_No3-03.pdf |
| _version_ | 1811261409460224000 |
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| author | APURBA K. BHATTACHARJEE KEITH A. CARVALHO DEJAN OPSENICA BOGDAN A. SOLAJA |
| author_facet | APURBA K. BHATTACHARJEE KEITH A. CARVALHO DEJAN OPSENICA BOGDAN A. SOLAJA |
| author_sort | APURBA K. BHATTACHARJEE |
| collection | DOAJ |
| description | A three-dimensional QSAR pharmacophore model for antimalarial activity of steroidal 1,2,4,5-tetraoxanes was developed from a set of 17 substituted antimalarial derivatives out of 27 analogues that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plasmodium falciparum malaria. The pharmacophore, which contains two hydrogen bond acceptors (lipid) and one hydrophobic (aliphatic) feature, was found to map well onto the potent analogues and many other well-known antimalarial trioxane drugs including artemisinin, arteether, artesunic acid, and tetraoxanes. The presence of at least one hydrogen bond acceptor in the trioxane or the tetraoxane moiety appears to be necessary for potent activity of this class of compounds. Docking calculations of some of these compounds with heme are consistent with the above observation as the proximity of the heme iron to the oxygen atom of the trioxane or the tetraoxane moiety favors potent activity of the compounds. Electron transfer from the oxygen of trioxane or the tetraoxane appears to be crucial for mechanism of action of the compounds. This information together with the pharmacophore should enable search for new peroxide containing antimalarial candidates from databases and custom designed synthesis of more efficacious and safer analogues. |
| first_indexed | 2024-04-12T19:02:45Z |
| format | Article |
| id | doaj.art-0bf17d6508a44fd1b8df5cd1ed8e967a |
| institution | Directory Open Access Journal |
| issn | 0352-5139 |
| language | English |
| last_indexed | 2024-04-12T19:02:45Z |
| publishDate | 2005-03-01 |
| publisher | Serbian Chemical Society |
| record_format | Article |
| series | Journal of the Serbian Chemical Society |
| spelling | doaj.art-0bf17d6508a44fd1b8df5cd1ed8e967a2022-12-22T03:20:05ZengSerbian Chemical SocietyJournal of the Serbian Chemical Society0352-51392005-03-01703329345Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational proceduresAPURBA K. BHATTACHARJEEKEITH A. CARVALHODEJAN OPSENICABOGDAN A. SOLAJAA three-dimensional QSAR pharmacophore model for antimalarial activity of steroidal 1,2,4,5-tetraoxanes was developed from a set of 17 substituted antimalarial derivatives out of 27 analogues that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plasmodium falciparum malaria. The pharmacophore, which contains two hydrogen bond acceptors (lipid) and one hydrophobic (aliphatic) feature, was found to map well onto the potent analogues and many other well-known antimalarial trioxane drugs including artemisinin, arteether, artesunic acid, and tetraoxanes. The presence of at least one hydrogen bond acceptor in the trioxane or the tetraoxane moiety appears to be necessary for potent activity of this class of compounds. Docking calculations of some of these compounds with heme are consistent with the above observation as the proximity of the heme iron to the oxygen atom of the trioxane or the tetraoxane moiety favors potent activity of the compounds. Electron transfer from the oxygen of trioxane or the tetraoxane appears to be crucial for mechanism of action of the compounds. This information together with the pharmacophore should enable search for new peroxide containing antimalarial candidates from databases and custom designed synthesis of more efficacious and safer analogues.http://www.shd.org.yu/HtDocs/SHD/vol70/No3/JSCS_V70_No3-03.pdfQSAR3D pharmacophoretetraoxanemalariasteroids |
| spellingShingle | APURBA K. BHATTACHARJEE KEITH A. CARVALHO DEJAN OPSENICA BOGDAN A. SOLAJA Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures Journal of the Serbian Chemical Society QSAR 3D pharmacophore tetraoxane malaria steroids |
| title | Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures |
| title_full | Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures |
| title_fullStr | Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures |
| title_full_unstemmed | Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures |
| title_short | Structure-activity relationship study of steroidal 1,2,4,5-tetraoxane animalarials using computational procedures |
| title_sort | structure activity relationship study of steroidal 1 2 4 5 tetraoxane animalarials using computational procedures |
| topic | QSAR 3D pharmacophore tetraoxane malaria steroids |
| url | http://www.shd.org.yu/HtDocs/SHD/vol70/No3/JSCS_V70_No3-03.pdf |
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