Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved]
Inositol phosphorylceramide synthase (IPCS) has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2016-09-01
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| Series: | F1000Research |
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| Online Access: | https://f1000research.com/articles/5-1610/v2 |
| _version_ | 1818291876688560128 |
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| author | Vineetha Mandlik Shailza Singh |
| author_facet | Vineetha Mandlik Shailza Singh |
| author_sort | Vineetha Mandlik |
| collection | DOAJ |
| description | Inositol phosphorylceramide synthase (IPCS) has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an important role in maintaining the infectivity and viability of the parasite. The present study explores the possibility of targeting IPCS; development of suitable inhibitors for the same would serve as a treatment strategy for the infectious disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these inhibitors were performed which provided insights into the binding modes of the inhibitors. In vitro screening of the top three compounds has resulted in the identification of one of the compounds (compound 3) which shows little cytotoxic effects. This compound therefore represents a good starting point for further in vivo experimentation and could possibly serve as an important drug candidate for the treatment of leishmaniasis. |
| first_indexed | 2024-12-13T02:51:02Z |
| format | Article |
| id | doaj.art-20d9b04815974798b16e52d390324132 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-13T02:51:02Z |
| publishDate | 2016-09-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-20d9b04815974798b16e52d3903241322022-12-22T00:02:03ZengF1000 Research LtdF1000Research2046-14022016-09-01510.12688/f1000research.9151.210109Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved]Vineetha Mandlik0Shailza Singh1National Centre for Cell Science, NCCS Complex, SP Pune University Campus, Pune, IndiaNational Centre for Cell Science, NCCS Complex, SP Pune University Campus, Pune, IndiaInositol phosphorylceramide synthase (IPCS) has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an important role in maintaining the infectivity and viability of the parasite. The present study explores the possibility of targeting IPCS; development of suitable inhibitors for the same would serve as a treatment strategy for the infectious disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these inhibitors were performed which provided insights into the binding modes of the inhibitors. In vitro screening of the top three compounds has resulted in the identification of one of the compounds (compound 3) which shows little cytotoxic effects. This compound therefore represents a good starting point for further in vivo experimentation and could possibly serve as an important drug candidate for the treatment of leishmaniasis.https://f1000research.com/articles/5-1610/v2Protein Chemistry & ProteomicsTropical & Travel-Associated Diseases |
| spellingShingle | Vineetha Mandlik Shailza Singh Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] F1000Research Protein Chemistry & Proteomics Tropical & Travel-Associated Diseases |
| title | Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] |
| title_full | Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] |
| title_fullStr | Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] |
| title_full_unstemmed | Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] |
| title_short | Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved] |
| title_sort | molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase inhibitor complex in leishmaniasis insight into the structure based drug design version 2 referees 2 approved |
| topic | Protein Chemistry & Proteomics Tropical & Travel-Associated Diseases |
| url | https://f1000research.com/articles/5-1610/v2 |
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