Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i>
Three new quinazoline-containing diketopiperazines, polonimides A–C (<b>1</b>–<b>3</b>), along with four analogues (<b>4</b>–<b>7</b>), were obtained from the marine-derived fungus <i>Penicillium polonicum</i>. Among them, <b>2</b&...
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MDPI AG
2020-09-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/9/479 |
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| author | Xing-Chen Guo Ya-Hui Zhang Wen-Bin Gao Li Pan Hua-Jie Zhu Fei Cao |
| author_facet | Xing-Chen Guo Ya-Hui Zhang Wen-Bin Gao Li Pan Hua-Jie Zhu Fei Cao |
| author_sort | Xing-Chen Guo |
| collection | DOAJ |
| description | Three new quinazoline-containing diketopiperazines, polonimides A–C (<b>1</b>–<b>3</b>), along with four analogues (<b>4</b>–<b>7</b>), were obtained from the marine-derived fungus <i>Penicillium polonicum</i>. Among them, <b>2</b> and <b>4</b>, <b>3</b> and <b>5</b> were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of <b>1</b>–<b>3</b> were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in <b>3</b> and <b>5</b>. All of <b>1</b>–<b>7</b> were tested for their chitinase inhibitory activity against <i>Of</i>Hex1 and <i>Of</i>Chi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds <b>1</b>–<b>7</b> exhibited weak activity towards <i>Of</i>Hex1 and strong activity towards <i>Of</i>Chi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%–10.3% and 79.1%–95.4%, respectively. Interestingly, <b>1</b>–<b>7</b> showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery. |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T16:10:43Z |
| publishDate | 2020-09-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-7c2c7b35f4f24c59aeb3754613883ad32023-11-20T14:30:37ZengMDPI AGMarine Drugs1660-33972020-09-0118947910.3390/md18090479Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i>Xing-Chen Guo0Ya-Hui Zhang1Wen-Bin Gao2Li Pan3Hua-Jie Zhu4Fei Cao5College of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, ChinaCollege of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, ChinaCoollege of Life Science, Cangzhou Normal University, Cangzhou 061001, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaCollege of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, ChinaCollege of Pharmaceutical Sciences, Institute of Life Science and Green Development, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, ChinaThree new quinazoline-containing diketopiperazines, polonimides A–C (<b>1</b>–<b>3</b>), along with four analogues (<b>4</b>–<b>7</b>), were obtained from the marine-derived fungus <i>Penicillium polonicum</i>. Among them, <b>2</b> and <b>4</b>, <b>3</b> and <b>5</b> were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of <b>1</b>–<b>3</b> were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in <b>3</b> and <b>5</b>. All of <b>1</b>–<b>7</b> were tested for their chitinase inhibitory activity against <i>Of</i>Hex1 and <i>Of</i>Chi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds <b>1</b>–<b>7</b> exhibited weak activity towards <i>Of</i>Hex1 and strong activity towards <i>Of</i>Chi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%–10.3% and 79.1%–95.4%, respectively. Interestingly, <b>1</b>–<b>7</b> showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.https://www.mdpi.com/1660-3397/18/9/479marine-derived fungus<i>Penicillium polonicum</i>quinazolinediketopiperazinebioactivity |
| spellingShingle | Xing-Chen Guo Ya-Hui Zhang Wen-Bin Gao Li Pan Hua-Jie Zhu Fei Cao Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> Marine Drugs marine-derived fungus <i>Penicillium polonicum</i> quinazoline diketopiperazine bioactivity |
| title | Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> |
| title_full | Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> |
| title_fullStr | Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> |
| title_full_unstemmed | Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> |
| title_short | Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus <i>Penicillium polonicum</i> |
| title_sort | absolute configurations and chitinase inhibitions of quinazoline containing diketopiperazines from the marine derived fungus i penicillium polonicum i |
| topic | marine-derived fungus <i>Penicillium polonicum</i> quinazoline diketopiperazine bioactivity |
| url | https://www.mdpi.com/1660-3397/18/9/479 |
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