Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells
Based on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-<i>O</i>-glucosides of NQs were prepared. A new method of conjugation of per-<i>O</i>-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene s...
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MDPI AG
2020-11-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/12/602 |
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| author | Sergey Polonik Galina Likhatskaya Yuri Sabutski Dmitry Pelageev Vladimir Denisenko Evgeny Pislyagin Ekaterina Chingizova Ekaterina Menchinskaya Dmitry Aminin |
| author_facet | Sergey Polonik Galina Likhatskaya Yuri Sabutski Dmitry Pelageev Vladimir Denisenko Evgeny Pislyagin Ekaterina Chingizova Ekaterina Menchinskaya Dmitry Aminin |
| author_sort | Sergey Polonik |
| collection | DOAJ |
| description | Based on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-<i>O</i>-glucosides of NQs were prepared. A new method of conjugation of per-<i>O</i>-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene spacer was developed. Methylation of 2-hydroxy group of quinone core of acetylthiomethylglycosides by diazomethane and deacetylation of sugar moiety led to 28 new thiomethylglycosidesof 2-hydroxy- and 2-methoxy-1,4-NQs. The cytotoxic activity of starting 1,4-NQs (13 compounds) and their <i>O</i>- and <i>S</i>-glycoside derivatives (37 compounds) was determined by the MTT method against Neuro-2a mouse neuroblastoma cells. Cytotoxic compounds with EC<sub>50</sub> = 2.7–87.0 μM and nontoxic compounds with EC<sub>50</sub> > 100 μM were found. Acetylated <i>O</i>- and <i>S</i>-glycosides 1,4-NQs were the most potent, with EC<sub>50</sub> = 2.7–16.4 μM. Methylation of the 2-OH group innaphthoquinone core led to a sharp increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC<sub>50</sub> > 100 μM. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives was constructed and tested. Descriptors related to the cytotoxic activity of new 1,4-NQ derivatives were determined. The QSAR model is good at predicting the activity of 1,4-NQ derivatives which are unused for QSAR models and nontoxic derivatives. |
| first_indexed | 2024-03-10T14:28:16Z |
| format | Article |
| id | doaj.art-86a559cc097c42bd99214db2892359a5 |
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| language | English |
| last_indexed | 2024-03-10T14:28:16Z |
| publishDate | 2020-11-01 |
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| series | Marine Drugs |
| spelling | doaj.art-86a559cc097c42bd99214db2892359a52023-11-20T22:49:21ZengMDPI AGMarine Drugs1660-33972020-11-01181260210.3390/md18120602Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer CellsSergey Polonik0Galina Likhatskaya1Yuri Sabutski2Dmitry Pelageev3Vladimir Denisenko4Evgeny Pislyagin5Ekaterina Chingizova6Ekaterina Menchinskaya7Dmitry Aminin8G.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry of Far Eastern Branch of Russian Academy of Sciences, Prospekt 100-let Vladivostoku, 159, 690022 Vladivostok, RussiaBased on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-<i>O</i>-glucosides of NQs were prepared. A new method of conjugation of per-<i>O</i>-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene spacer was developed. Methylation of 2-hydroxy group of quinone core of acetylthiomethylglycosides by diazomethane and deacetylation of sugar moiety led to 28 new thiomethylglycosidesof 2-hydroxy- and 2-methoxy-1,4-NQs. The cytotoxic activity of starting 1,4-NQs (13 compounds) and their <i>O</i>- and <i>S</i>-glycoside derivatives (37 compounds) was determined by the MTT method against Neuro-2a mouse neuroblastoma cells. Cytotoxic compounds with EC<sub>50</sub> = 2.7–87.0 μM and nontoxic compounds with EC<sub>50</sub> > 100 μM were found. Acetylated <i>O</i>- and <i>S</i>-glycosides 1,4-NQs were the most potent, with EC<sub>50</sub> = 2.7–16.4 μM. Methylation of the 2-OH group innaphthoquinone core led to a sharp increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC<sub>50</sub> > 100 μM. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives was constructed and tested. Descriptors related to the cytotoxic activity of new 1,4-NQ derivatives were determined. The QSAR model is good at predicting the activity of 1,4-NQ derivatives which are unused for QSAR models and nontoxic derivatives.https://www.mdpi.com/1660-3397/18/12/602neuroblastoma Neuro-2a cells5,8-dihydroxy-1,4-naphthoquinone<i>O</i>-glucosidethiomethylglycosidecytotoxic activityQSAR |
| spellingShingle | Sergey Polonik Galina Likhatskaya Yuri Sabutski Dmitry Pelageev Vladimir Denisenko Evgeny Pislyagin Ekaterina Chingizova Ekaterina Menchinskaya Dmitry Aminin Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells Marine Drugs neuroblastoma Neuro-2a cells 5,8-dihydroxy-1,4-naphthoquinone <i>O</i>-glucoside thiomethylglycoside cytotoxic activity QSAR |
| title | Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells |
| title_full | Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells |
| title_fullStr | Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells |
| title_full_unstemmed | Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells |
| title_short | Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their <i>O</i>- and <i>S</i>-Glycoside Derivatives Tested against Neuro-2a Cancer Cells |
| title_sort | synthesis cytotoxic activity evaluation and quantitative structure activityanalysis of substituted 5 8 dihydroxy 1 4 naphthoquinones and their i o i and i s i glycoside derivatives tested against neuro 2a cancer cells |
| topic | neuroblastoma Neuro-2a cells 5,8-dihydroxy-1,4-naphthoquinone <i>O</i>-glucoside thiomethylglycoside cytotoxic activity QSAR |
| url | https://www.mdpi.com/1660-3397/18/12/602 |
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