CHIRALITY
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2013
·Vol. 25
·期 10
·656-662
·
IF 1.894
Yangmin Ma,Hao Wu,Jin Zhang,Yanchao Li
A series of single isomers tetrahydro- β -carboline diketopiperazines were stereoselectively synthesized starting from l -tryptophan methyl ester hydrochloride and six aldehydes through a four-step reaction including Pictet-Spengler reaction, crystallization-induced asymmetric transformations (CIAT), Schotten-Baumann reaction, and intramolecular ester amidation. The chemical structures were characterized by nuclear magnetic resonance (NMR) and elemental analysis, among which two compounds were determined by x-ray single crystal diffraction. Moreover, antimicrobial activities of all the compounds were also tested. Chirality 25:656–662, 2013 . © 2013 Wiley Periodicals, Inc.
研究领域:
有机化学
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药物化学
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微生物学
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PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Qiyue Wang,Gujie Mi,Daniel Hickey,Yanan Li,Jiasheng Tu,Thomas J. Webster,Yan Shen
Pneumonia is a major contributor to infection-based hospitalizations and deaths in the United States. Antibiotics such as azithromycin (AZM), although effective at managing pneumonia, often suffer from off-target diffusion and poor bioavailability when administered orally or via intravenous injection. The formation of biofilms at the disease sites makes the treatment more complicated by protecting bacteria from antimicrobial agents and thus necessitating a much higher dosage of antibiotics to eradicate the biofilms. As such, targeted pulmonary delivery of antibiotics has emerged as a promising alternative by providing direct access to the lung while also allowing higher local therapeutic concentrations but minimal systemic exposure. In this study, AZM was encapsulated in N-fumaroylated diketopiperazine (FDKP) microparticles for efficient pulmonary delivery. Both in vitro and in vivo results demonstrated that AZM@FDKP-MPs administered via intratracheal insufflation achieved at least a 3.4 times higher local concentration and prolonged retention times compared to intravenous injection and oral administration, suggesting their potential to better manage bacterial pneumonia.
研究领域:
药学
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微生物学
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呼吸病学
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DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
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2017
·
IF 1.828
Wei-Xun Chunyu,Zhang-Gui Ding,Jiang-Yuan Zhao,Yong-Xia Wang,Xiu-Lin Han,Ming-Gang Li,Meng-Liang Wen
Two new diketopiperazines, named diphenylalazine C (1) and epicoccin U (2), together with six known compounds (3–8) were isolated from the EtOAc extract of the fermentation broth of the tin mine tailings-derived fungus Schizophyllum commune YIM DT 10058. Their structures were elucidated by detailed analysis of spectroscopic data and comparison with related known compounds. Compounds 1 and 2 exhibited weak antibacterial and cytotoxic activities.
研究领域:
真菌学
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天然产物化学
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药物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2014
·
IF 3.432
Shengrong Liao,Xiaochu Qin,Ding Li,Zhengchao Tu,Jinsheng Li,Xuefeng Zhou,Junfeng Wang,Bin Yang,Xiuping Lin,Juan Liu,Xianwen Yang,Yonghong Liu
Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC 50 = 0.5–4.5 μM), especially to the cancer cell lines U937 (IC 50 = 0.5 μM) and K562 (IC 50 = 0.9 μM). Compound 4m could become a lead compound for further development for anticancer agents .
研究领域:
药物化学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Jialin Xie,Wentao Xu,Hongjian Song,Yuxiu Liu,Jingjing Zhang,Qingmin Wang
On the basis of the mechanism of acylhydrazone compounds inhibiting the assembly of TMV CP and the unique structural characteristics of diketopiperazine ring, a series of optically pure indole diketopiperazine acylhydrazone were designed and synthesized. In order to systematically study the effect of the spatial configuration of the compounds on the antiviral activity, four compounds with different spatial configurations at C6 and C12a were also prepared. The bioassay results indicated that most of these new compounds displayed moderate to good antiviral activity, among which compounds 23, 25, 27, 28, 31, and 5d showed a significantly higher activity than that of commercial ribavirin. An in-depth structure–activity relationship investigation showed that the spatial conformation was one of the most important factors in adjusting antiviral activity; the research results provided information about the possible optimum configuration for interaction of this molecular with its target protein. At the same time, these new compounds also exhibited broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. What’s more, some of these compounds exhibited good insecticidal activity to Plutella xylostella and Culex pipiens pallens.
研究领域:
有机化学
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植物保护
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2023
·
IF 3.8
Qi Hong,Miao-Miao Guo,Jin Yang,Xing Wei,Li Liao,Xiu-Juan Xin,Di Zhang,Fa-Liang An
Four previously undescribed diketopiperazine-type alkaloids including one oxepin-containing diketopiperazine-type alkaloid, oxepinamide L (1), three 4-quinazolinone alkaloids, puniceloids E-G (10–12), together with 12 known analogues, protuboxepin D (2), oxepinamides D-G, J-K and I (3–9), puniceloids B-D (13–15) and protubonine B (16), were isolated from the culture of the marine-derived fungus Aspergillus puniceus FAHY0085. The structures of the previously undescribed compounds were comprehensively elucidated by detailed interpretation of their NMR and HRESIMS data. Their absolute configurations were unambiguously determined by ROESY experiments, Marfey's method, calculated ECD experiments and single-crystal X-ray diffraction analysis. Compounds (3–4, 6–8, 14–15) were evaluated for their cytotoxic activity against HepG2, MCF-7, SW1116 and HeLa cells and compound 6 and 14 showed moderate cytotoxic activity against HeLa cells with IC 50 49.61 ± 2.91 and 28.38 ± 1.57 μM, respectively. Compounds (1–8, 11–15) were screened for their transcriptional activation of liver X receptor α and compound 11 with known compounds 13–15 showed significant transcriptional activation of liver X receptor α with EC 50 values in the range 2–50 μM.
研究领域:
化学
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药理学
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分子生物学
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PubMed
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SCIENCE OF THE TOTAL ENVIRONMENT
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2021
·
IF 7.963
Ji Liu,Wei Zhao,Shuang-wei Yang,Bin Hu,Ming-xin Xu,Shan-Wei Ma,Qiang Lu
Incineration of food waste leads to the release of NO x pollutants, whereas the formation mechanism of the NO x precursors (HCN, NH 3 , and HNCO) during the initial pyrolysis process is far from well-studied, limiting the source control on NO x release. In this work, 2,5-diketopiperazine (DKP) was selected as the N-containing model compound to study the formation mechanism of NO x precursors in food waste pyrolysis, by combining experiments and density functional theory (DFT) calculations. The C1-N2 bond broken via the N2-to-N5 H-transfer possesses the lowest energy barrier, together with the largest reaction rate constants in the range of 400–800 °C. NH 3 can be easily generated with low energy barriers and high rate constants at low temperatures (below 630 °C). Whereas, the rate constants of the pathways for HCN formation will exceed those for NH 3 generation in the range of 630–740 °C. In addition, the DKP pyrolysis can also lead to the formation of HNCO with a very low energy barrier, and it can convert into HCN and NH 3 through further hydrogenation and decomposition. These calculation results are exactly consistent with the experimental results that NH 3 was the main precursor in the range of 400–600 °C, and the yield of HCN exceeded that of NH 3 when the temperature was over 600 °C. Our current work on the formation mechanism of NO x precursors during the pyrolysis of DKP can provide theoretical guidance for the development of NO x control technology in the pyrolysis/combustion process of organic waste.
研究领域:
环境科学
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化学工程
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能源科学
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PubMed
高影响因子
Frontiers in Chemistry
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2019
·
IF 3.782
Jia Bin,Ma Yang-min,Liu Bin,Chen Pu,Hu Yan,Zhang Rui
Strategies for the synthesis of indole diketopiperazine alkaloids (indole DKPs) have been described and involve three analogs of indole DKPs. The antimicrobial activity and structure-activity relationship (SAR) of 24 indole DKPs were explored. Compounds 3b and 3c were found to be the most active, with minimum inhibitory concentrations (MIC) values in the range of 0.94–3.87 μM (0.39–1.56 μg/mL) against the four tested bacteria (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli). Furthermore, compounds 4a and 4b displayed broad-spectrum antimicrobial activity with MIC values of 1.10–36.9 μM (0.39–12.5 μg/mL) against all tested bacteria and plant pathogenic fungi (Colletotrichum gloeosporioides, Valsa mali, Alternaria alternata and Alternaria brassicae). According to the in silico study, compounds 3c showed significant binding affinity to the FabH protein from Escherichia coli, which has been identified as the key target enzyme of fatty acid synthesis (FAS) in bacteria. Therefore, these compounds are not only promising new antibacterial agents but also potential FabH inhibitors.
研究领域:
药物化学
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微生物学
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计算生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 63
·51020-51026
·
IF 3.84
Shengrong Liao,Ying Xu,Yong Tang,Junfeng Wang,Xuefeng Zhou,Liang Xu,Yonghong Liu
A small library of soluble 2,5-diketopiperazine derivatives were designed, synthesized and evaluated as antifouling agents against two species of marine organisms: Balanus amphitrite and Bugula neritina by larval attachment assay. The results showed that different derivatives had different antifouling activities. Among these compounds, 3a (EC50 = 2.5 μg mL−1), 3b (EC50 = 3.2 μg mL−1) and 3d (EC50 = 1.6 μg mL−1) had strong activities, and 2d (EC50 = 20.5 μg mL−1), 3l (EC50 = 25.0 μg mL−1) and 3m (EC50 = 18.5 μg mL−1) had moderate activities against Balanus amphitrite, but other compounds had no activities. Differently, compounds 3d (EC50 = 3.1 μg mL−1) and 3i (EC50 = 2.3 μg mL−1) exhibited strong activities, and 3a (EC50 = 11.3 μg mL−1) and 3c (EC50 = 17.2 μg mL−1) showed moderate activities against Bugula neritina, whereas other compounds had no activities. All of the active compounds had stronger antifouling activities than those of the natural product cyclo-(L-Phe-L-Pro). Compound 3d could be a new template molecule for further development as an antifouling agent because of its strong inhibitory activities against both species of fouling organisms with low or no toxicity to the environment.
研究领域:
海洋生物学
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药物化学
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环境科学
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DOI
高影响因子
PHYTOCHEMISTRY
·
2025
·
IF 3.4
Junguo Huang,Shan Ran,Guanghui Yang,Liangxiu Liao,Di Li,Qingpei Liu,Wenjing Wang,Xiaolong Yang
Five previously undescribed compounds, including one di- nor -lanostanoid aspverslanostane A ( 1 ), one indole diketopiperazine (indole DKP) alkaloid aspversamide A ( 2 ), and three itaconic acid derivatives asperitaconic acids D–F ( 13 – 15 ), along with 15 previously identified compounds, are isolated from the endophytic fungus Aspergillus versicolor HYQZ-324. The structures of compounds are elucidated via comprehensive spectroscopic analyses and electronic circular-dichroism calculations. Aspverslanostane A ( 1 ) represents the first example of a naturally occurring triterpene both with the 28- and 29-methyl groups demethylated. Aspversamide A ( 2 ) exhibits a distinctive skeletal structure of indole DKPs, characterised by an additional benzofuranone moiety at C-8. The compounds selected are subjected to anti-bacterial activity assays against eight clinically resistant bacteria, and none of the compounds exhibit satisfactory activity.
研究领域:
天然产物化学
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微生物学
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药理学
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DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 7
·289
·
IF 5.4
Shijie Bi,Yating Cao,Shiyuan Fang,Yanyan Chu,Zixuan Zhang,Meng Li,Rilei Yu,Jinbo Yang,Yu Tang,Peiju Qiu
The internal tandem duplication mutation of FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with high recurrence and mortality rates in acute myeloid leukemia (AML), making it a critical target for anti-AML therapies. Plinabulin is a diketopiperazines derivative that exhibits extensive anti-cancer potency by targeting β-tubulin. We designed and synthesized a novel FLT3 inhibitor, namely5-3, based on the structure of plinabulin and evaluated its effect on FLT3-ITD mutant AML cells. The results indicated that5-3potently and selectively inhibits the growth of mutant FLT3-expressingleukemia cells, and had no effect on FLT3 wide-type cancer cells, suggesting the antiproliferative activity of5-3depends highly on FLT3-ITD expression. Mechanically,5-3significantly suppressed the phosphorylation of FLT3 signaling pathway, including STAT5, Erk and Akt. Moreover, the efficiency of compound5-3is not associated with Plinabulin’s typical target, β-tubulin. In conclusion, the study identified diketopiperazine derivative as a novel FLT3-ITD selective inhibitor. These results demonstrated that5-3might be a drug candidate for the treatment of FLT3-ITD-positive AML.
研究领域:
肿瘤学
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药物化学
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分子生物学
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血液学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2024
·
IF 3.2
Zhibo Hu,Haishan Cui,Qiang Wang,Cheng Li,Senhua Chen,Zhizeng Gao,Lan Liu,Bo Peng,Jing Li
Seven previously undescribed compounds, including four diketomorpholine alkaloids ( 1 ‒ 4 ), one indole diketopiperazine alkaloid ( 9 ), one chromone ( 10 ), and one benzoic acid derivative ( 13 ), and nine known compounds ( 5 – 8 , 11 , 12 , and 14 – 16 ) were isolated from two different fungal sources. Nine of these metabolites ( 1 – 9 ) were obtained from a seagrass-derived Aspergillus alabamensis SYSU-6778, while the others were obtained from a mixed culture of A. alabamensis SYSU-6778 and a co-isolated fungus A . fumigatiaffinis SYSU-6786. The chemical structures of the compounds were deduced via spectroscopic techniques (including HRESIMS, 1D and 2D NMR), chemical reactions, and ECD calculations. It is worth noting that compound 10 was identified as a defensive secondary metabolite of strain SYSU-6786, produced through the induction of compound 8 under co-culture conditions. Compounds 3 and 4 possessed a naturally rare isotryptophan core. Moreover, compounds 1 and 2 exhibited potent inhibitory activities against fish pathogenic bacterium Edwardsiella ictalurid, with minimum inhibitory concentration values of 10.0 μg/mL for both compounds.
研究领域:
微生物学
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植物化学
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生物技术
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药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）