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Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum

Three new quinazoline-containing diketopiperazines, polonimides A–C (1–3), along with four analogues (4–7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configuratio...

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Autores principales: Guo, Xing-Chen, Zhang, Ya-Hui, Gao, Wen-Bin, Pan, Li, Zhu, Hua-Jie, Cao, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551877/
https://www.ncbi.nlm.nih.gov/pubmed/32967228
http://dx.doi.org/10.3390/md18090479
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author Guo, Xing-Chen
Zhang, Ya-Hui
Gao, Wen-Bin
Pan, Li
Zhu, Hua-Jie
Cao, Fei
author_facet Guo, Xing-Chen
Zhang, Ya-Hui
Gao, Wen-Bin
Pan, Li
Zhu, Hua-Jie
Cao, Fei
author_sort Guo, Xing-Chen
collection PubMed
description Three new quinazoline-containing diketopiperazines, polonimides A–C (1–3), along with four analogues (4–7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1–3 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 3 and 5. All of 1–7 were tested for their chitinase inhibitory activity against OfHex1 and OfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1–7 exhibited weak activity towards OfHex1 and strong activity towards OfChi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%–10.3% and 79.1%–95.4%, respectively. Interestingly, 1–7 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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spelling pubmed-75518772020-10-14 Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum Guo, Xing-Chen Zhang, Ya-Hui Gao, Wen-Bin Pan, Li Zhu, Hua-Jie Cao, Fei Mar Drugs Article Three new quinazoline-containing diketopiperazines, polonimides A–C (1–3), along with four analogues (4–7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1–3 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 3 and 5. All of 1–7 were tested for their chitinase inhibitory activity against OfHex1 and OfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1–7 exhibited weak activity towards OfHex1 and strong activity towards OfChi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%–10.3% and 79.1%–95.4%, respectively. Interestingly, 1–7 showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery. MDPI 2020-09-21 /pmc/articles/PMC7551877/ /pubmed/32967228 http://dx.doi.org/10.3390/md18090479 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Xing-Chen
Zhang, Ya-Hui
Gao, Wen-Bin
Pan, Li
Zhu, Hua-Jie
Cao, Fei
Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title_full Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title_fullStr Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title_full_unstemmed Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title_short Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum
title_sort absolute configurations and chitinase inhibitions of quinazoline-containing diketopiperazines from the marine-derived fungus penicillium polonicum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551877/
https://www.ncbi.nlm.nih.gov/pubmed/32967228
http://dx.doi.org/10.3390/md18090479
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