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

Three new quinazoline-containing diketopiperazines, polonimides A-C ( - ), along with four analogues ( - ), were obtained from the marine-derived fungus . Among them, and , and were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of -...

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Bibliographic Details
Published in:Marine drugs 2020-09, Vol.18 (9), p.479
Main Authors: Guo, Xing-Chen, Zhang, Ya-Hui, Gao, Wen-Bin, Pan, Li, Zhu, Hua-Jie, Cao, Fei
Format: Article
Language:English
Subjects:
bioactivity
Cell Line, Tumor
Chitinases - antagonists & inhibitors
Circular Dichroism
diketopiperazine
Diketopiperazines - chemistry
Diketopiperazines - isolation & purification
Diketopiperazines - pharmacology
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - isolation & purification
Enzyme Inhibitors - pharmacology
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - pathology
Magnetic Resonance Spectroscopy
marine-derived fungus
Penicillium - metabolism
Penicillium polonicum
Prazosin - analogs & derivatives
quinazoline
Quinazolines - chemistry
Quinazolines - isolation & purification
Quinazolines - pharmacology
Stomach Neoplasms - drug therapy
Stomach Neoplasms - pathology
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
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Summary:Three new quinazoline-containing diketopiperazines, polonimides A-C ( - ), along with four analogues ( - ), were obtained from the marine-derived fungus . Among them, and , and were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of - 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 and . All of - were tested for their chitinase inhibitory activity against Hex1 and Chi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds - exhibited weak activity towards Hex1 and strong activity towards 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, - showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.
ISSN:1660-3397
1660-3397
DOI:10.3390/md18090479