查找使用阿拉丁产品的科研文献

Design, Synthesis and Antifungal Activity of Phloroglucinol Derivatives

Yang Meizhu,Lai Weihong,Li Junjian,Ye Lianbao

Phloroglucinols of Dryopteris fragrans (L.) Schott plant show strong antifungal activity. In previous work, we isolated a wide range of phloroglucinols from the plant and found that pseudoaspidinol of D. fragrans and its structural modifications (methylphloroglucinol derivatives) showed stronger antifungal activity and confirmed that the butyryl group of these compounds accounted for this activity. In this study, we designed a series of phloroglucinol derivatives ( A1–A9) and methylphloroglucinol derivatives ( B1–B9) by introducing acyl groups with diverse carbon numbers in the C-2 position, synthesized these compounds, and evaluated the anti-dermatophyte activity of compounds A1–A5 and B1–B5 on Trichophyton rubrum and Trichophyton mentagrophytes fungal species. The results showed that compound A5 exhibited the strongest activity. These compounds can be used as leads for the development of new antifungal agents.

Biochemical investigations of polyphenol degradation enzymes in the phototrophic bacterium Rubrivivax gelatinosus

Cui Mengyu,Wei Yifeng,Tan Jason,Li Tong,Jiao Xinan,Zhou Yan

Phloroglucinol (1,3,5-trihydroxybenzene) is an important intermediate in the degradation of flavonoids and tannins by anaerobic bacteria. Recent studies have shed light on the enzymatic mechanism of phloroglucinol degradation in butyrate-forming anaerobic bacteria, including environmental and intestinal bacteria such as Clostridium and Flavonifractor sp. Phloroglucinol degradation gene clusters have also been identified in other metabolically diverse bacteria, although the polyphenol metabolism of these microorganisms remain largely unexplored. Here, we describe biochemical studies of polyphenol degradation enzymes found in the purple non-sulfur bacterium Rubrivivax gelatinosus IL144, an anaerobic photoheterotroph reported to utilize diverse organic compounds as carbon sources for growth. In addition to the phloroglucinol reductase and dihydrophloroglucinol cyclohydrolase that catalyze phloroglucinol degradation, we characterize a Mn2+-dependent phloretin hydrolase that catalyzes the cleavage of phloretin into phloroglucinol and phloretic acid. We also report a Mn2+-dependent decarboxylase (DeC) that catalyzes the reversible decarboxylation of 2,4,6-trihydroxybenzoate to form phloroglucinol. A bioinformatics search led to the identification of DeC homologs in diverse soil and gut bacteria, and biochemical studies of a DeC homolog from the human gut bacterium Flavonifractor plautii demonstrated that it is also a 2,4,6-trihydroxybenzoate decarboxylase. Our study expands the range of enzymatic mechanisms for phloroglucinol formation, and provides further biochemical insight into polyphenol metabolism in the anaerobic biosphere.

Anaerobic phloroglucinol degradation by Clostridium scatologenes

Yan Zhou,Yifeng Wei,Li Jiang,Xinan Jiao,Yan Zhang

New expression system to increase the yield of phloroglucinol

Shan Yuan,Rubing Zhang,Yujin Cao,Jing Guo,Mo Xian,Wei Liu

Phloroglucinol (PG) is an important chemical that has been produced in engineered E. coli. Low yield and high cost are the bottlenecks that limit the industrialisation and popularisation of PG biosynthesis. In this study, a new expression system (pNEW vector) was developed for PG biosynthesis by using inexpensive p-isopropylbenzoate (cumate) as the inducer, and the copy number control element (rop) was added to optimise the original pNEW vector, which not only promoted the PG yield, but also reduced the leakage expression. Compared to traditional IPTG inducible expression system, 2-fold enhancement of PG yield was obtained with optimised expression system and the cost of inducer was reduced to 1/9. These results provide technical support for the biosynthesis of PG and reference for the selection of induced expression systems for other chemical biosynthesis.

An aldolase-dependent phloroglucinol degradation pathway in Collinsella sp. zg1085

Yating Li,Tong Xu,Yanqin Tu,Tong Li,Yifeng Wei,Yan Zhou

Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.

Metabolic engineering of E. coli for producing phloroglucinol from acetate

Yu Shengzhu,Guo Liwei,Zhao Luyao,Chen Zhenya,Huo Yixin

Phloroglucinol is a three-hydroxyl phenolic compound and has diverse physiological and pharmacological activities such as antivirus and anti-inflammatory activities. Chemical synthesis of phloroglucinol suffered from many drawbacks such as high cost and environmental pollution. To avoid the above issues, microbial phloroglucinol biosynthesis was successfully accomplished in this study, while the abundant and low-cost acetate was used as the main carbon source. Firstly, the toxicity of phloroglucinol was tested, and E. coli BL21(DE3) could tolerate 5 g/L phloroglucinol. The ability of phloroglucinol synthase (PhlD) for catalyzing malonyl-CoA to phloroglucinol was confirmed, and E. coli BL21(DE3) expressing PhlD and acetyl-CoA carboxylase (ACCase) could produce 1107 ± 12 mg/L phloroglucinol from glucose. Then, E. coli BL21(DE3) was engineered to utilize acetate to produce 228 ± 15 mg/L phloroglucinol. Then, the endogenous citrate synthase (GltA) which could catalyze oxaloacetate and acetyl-CoA generated from acetate to citrate was knocked down by CRISPRi system in order to enhance the carbon flux for phloroglucinol production, and the titer was improved to 284 ± 8 mg/L. This work demonstrated that acetate could be used as low-cost substrate to achieve the biosynthesis of phloroglucinol and provided an example of effective utilization of acetate.

Antifungal Effects of the Phloroglucinol Derivative DPPG Against Pathogenic Aspergillus fumigatus

Liyang Wang,Junying He,Hanzhong Feng,Qian Li,Meirong Song,Haoran Gou,Yongxing He,Kui Zhu

Background:Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens.Methods:We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG onAspergillus fumigatuswas investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in aGalleria mellonellainfection model.Results:We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity againstAspergillusspp. andCandidaspp. but also impaired hyphal growth and spore germination ofA. fumigatusin vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in aG. mellonellainfection model.Conclusions:Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections.

Theoretical calculation guided molecularly imprinted polymer for selective adsorption of phloroglucinol

Ximin Chen,Long Jiang,Yaojie Liu,Lulu Zhang,Debin Yang,Xiaomeng Su,Zongjiang Yu,Mo Xian,Chao Xu

Effective adsorption of phloroglucinol (PG) is a method that kills two birds with one stone, which can not only reduce the harm of phenolic wastewater to the environment but also bring considerable economic benefits. In this work, the optimal functional monomer N-Vinyl imidazole (VIM) that possesses the strongest affinity with PG among 11 phenolic monomers was quantitatively selected by DFT calculation. The key factors that influence the adsorption capacity (Q e ) and imprinting effect ( α ) were systematically researched. And the physicochemical property and morphology of the obtained VIM-MIP with the best adsorption performance were explored by a series of characterization methods. The adsorption tests were carried out, indicating that the VIM-MIP exhibited a large adsorption capability (Q e = 81.34 mg/g), which exceeded 78.97 % of the existing optimal absorbents for PG. What’s more, the adsorption data for PG fit in with the Freundlich model (R 2 > 0.99). More notably, the excellent PG selectivity of the VIM-MIP was confirmed by competitive adsorption experiments under binary systems (relative selectivity coefficient, 2.014), which was attributed to the existence of imprinted cavities. The molecular simulation, X-ray photoelectron spectroscopy (XPS) analysis, and Zeta potential analysis were employed to reveal the adsorption mechanism, indicating the hydrogen bond was the main driving force.

Exploring two types of prenylated bitter compounds from hop plant (Humulus lupulus L.) against α-glucosidase in vitro and in silico

Limin Wang,Yunsen Zhang,I. Agbaka Johnpaul,Kai Hong,Yumei Song,Xiao Yang,Chenyan Lv,Changwei Ma

Hops are abundant in natural bioactive compounds. In this work, nine prenylated bitter compounds from hop were evaluated for their inhibitory activity against α-glucosidase. As a result, four flavonoids and one phloroglucinol (lupulone, LP) outperformed acarbose in inhibiting α-glucosidase. Isoxanthohumol (IX) and LP with two types of structures were selected for inhibition mechanism studies by spectroscopic methods and molecular dynamics simulation (MD). Results showed that IX acted as noncompetitive inhibitor and bound to α-glucosidase in allosteric sites via hydrogen bonds, hydrophobic, van der Waals (vdW), and electrostatic force, whereas LP was uncompetitive inhibitor and bound to catalytic sites via hydrophobic and vdW interactions. Notably, the conformation around binding site of α-glucosidase formed stable α-helix and tightened after binding IX and LP, respectively, which helped to elucidate noncompetitive and uncompetitive inhibitory mechanisms. This work demonstrated that two types of prenylated bitter compounds are discrepant in their mechanisms of interaction with α-glucosidase.

Phloroglucinol derivatives as anti-tumor agents: synthesis, biological activity evaluation and molecular docking studies

Zhang Fuli,Lai Qingfu,Lai Weihong,Li Ming,Jin Xiaobao,Ye Lianbao

Phloroglucinol compounds isolated from Dryopteris fragrans (L.) Schott showed a variety of biological activities, such as anticancer and anti-inflammatory. In this study, we have made a number of modifications around the scaffold of phloroglucinol and synthesized phloroglucinol derivatives A1–A9, B1–B9 , and C1–C3 . We synthesized these compounds and investigated their effect on four human cancer cell lines (A-549, MCF-7, Hela, HepG2 cell lines) via MTT assay in vitro. The results revealed that all compounds exhibited certain antiproliferative activities on cancer cell lines and excellent inhibitory effects on MCF-7, in which compound C2 was the best with the IC 50 value of 18.49 μM, exceeding that of 5-fluorouracil. Moreover, the cell apoptosis test showed that compound C2 induced apoptosis in a concentration-dependent manner. Furthermore, the results of molecular docking analysis explained the probable interaction between the active compounds and active sites of target protein 4I22 and 1OG5.

Phloroglucinol, a clinical-used antispasmodic, inhibits amyloid aggregation and degrades the pre-formed amyloid proteins

Yanfei Xie,Jiani Lu,Tiantian Yang,Chao Chen,Yongjie Bao,Luying Jiang,Hua Wei,Xiang Wu,Li Zhao,Shan He,Dongdong Lin,Fufeng Liu,Hao Liu,Xiaojun Yan,Wei Cui

Amyloid proteins, such as β-amyloid (Aβ) and α-synuclein (α-syn), could form neurotoxic aggregates during the progression of neurodegenerative disorders. Phloroglucinol, a clinical-used drug for treating spasmodic pain, was predicted to cross the blood brain-barrier and possesses neuroprotective potential. In this study, we have found, for the first time, that phloroglucinol inhibited the formation of amyloid aggregates, and degraded pre-formed amyloid aggregates with the similar efficacy as curcumin, a widely known amyloid aggregation inhibitor. Moreover, phloroglucinol decreased the seeding during aggregation process and inhibited the aggregation of Aβ 1 – 42 with homocysteine (Hcy) seeds. Molecular docking analysis further demonstrated hydrophobic interactions and hydrogen bonds between phloroglucinol and Aβ 1 – 42 /α-syn. Furthermore, phloroglucinol inhibited amyloid aggregates-induced cytotoxicity in neuronal cells and prevented Aβ 1 – 42  + Hcy aggregates-induced cognitive impairments in mice. All these results suggested that phloroglucinol possesses the ability to degrade pre-formed amyloid aggregates, to inhibit the seeding during amyloid aggregation, and to reduce the neurotoxicity, indicating the reposition possibility of phloroglucinol as a novel drug for treating neurodegenerative disorders.

Synthesis of one-dimensional silver nanowires in aqueous solution using phloroglucinol as a reducing reagent

Yecheng Lu,Wenlong Wang,Ruijing Li,Shilong Wang,Cheng Wang

Silver nanowires (AgNWs) are promising alternatives to indium tin oxide (ITO) transparent electrodes due to their favorable electrical and optical properties. Herein, high-quality AgNWs with an average diameter of 32 nm and an ultrahigh aspect ratio of 3000 were synthesized via a hydrothermal process at 160 °C using phloroglucinol, a typical polyhydroxyphenol, as the reducing agent. In an aqueous reaction system, in situ formed AgCl colloids gradually evolved into polyhedral particles during the reaction. Based on the observed morphology evolution, these AgCl-derived structures are suggested to participate in the formation process of AgNWs, possibly by influencing the distribution and interfacial evolution of silver species. Key synthetic parameters, including the reaction temperature/time, polyvinylpyrrolidone (PVP) molecular weight, and the concentrations of phloroglucinol and chloride ions, were systematically investigated. These factors were found to affect the formation of AgNWs, likely through their influence on the reduction behavior of Ag+ in the reaction system. Transparent conductive films (TCFs) fabricated from these AgNWs exhibited tunable optoelectronic properties depending on the deposition amount. In the high-transmittance region, the films showed a balanced combination of sheet resistance, transmittance, haze, and the figure of merit. For example, at 90% transmittance, the film exhibited a sheet resistance of 45.15 Ω sq−1 with low haze (2%), while increased coating density led to reduced sheet resistance but higher haze (4.8%). These results indicate that the obtained AgNWs have potential for transparent conductive film applications.