TETRAHEDRON
·
2023
·
IF 2.1
Zifan Zhu,Xiaoqing Feng,Hecheng Wang,Jiaru Fan,Chen Zhang,Guoqiang Song,Long Tang
Coumarin and chalcone are two compounds that have been extensively studied for their neuroprotective effects. Coumarin is known for its ability to inhibit MAO activity in the brain and reduce central nervous system damage caused by dopamine degradation. Chalcone, on the other hand, has gained attention due to its potential medicinal value, including free radical scavenging, anti-inflammatory, and neuroprotective properties. Both compounds have shown promise in the development of treatments for neurodegenerative diseases like Alzheimer's disease . In this study, we designed and synthesized 36 coumarin-chalcone heteroderivatives based on the principle of structure hybridization . We then evaluated the inhibitory effects of these compounds on phosphodiesterase II (PDE2) at the enzyme level and analyzed their structure-activity relationship. Among the hybrid derivatives, compounds 2b , 3a , 3i , 3m , and 1l demonstrated significant inhibitory activity on PDE2, with IC50 values of 24.46 μM , 16.82 μM , 28.13 μM , 21.88 μM , and 29.72 μM , respectively. This paper presents the design, synthesis, and biological evaluation of coumarin-chalcone hybrid derivatives for their potential as PDE2 inhibitors.
研究领域:
药物化学
·
神经科学
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DOI
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-12
·
IF 4.38
Tang Long,Jiang Jianchun,Song Guoqiang,Wang Yajing,Zhuang Ziheng,Tan Ying,Xia Yan,Huang Xianfeng,Feng Xiaoqing
A series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1 H NMR, 13 C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6 H -benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6 H -benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC 50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.
研究领域:
药物化学
·
生物化学
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DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 11
·3452
·
IF 4.927
Meng-Xing Huang,Yan-Quan Chen,Run-Duo Liu,Yue Huang,Chen Zhang
Dipyridamole, apart from its well-known antiplatelet and phosphodiesterase inhibitory activities, is a promising old drug for the treatment of pulmonary fibrosis. However, dipyridamole shows poor pharmacokinetic properties with a half-life (T1/2) of 7 min in rat liver microsomes (RLM). To improve the metabolic stability of dipyridamole, a series of pyrimidopyrimidine derivatives have been designed with the assistance of molecular docking. Among all the twenty-four synthesized compounds, compound(S)-4hshowed outstanding metabolic stability (T1/2= 67 min) in RLM, with an IC50of 332 nM against PDE5. Furthermore, some interesting structure–activity relationships (SAR) were explained with the assistance of molecular docking.Keywords:dipyridamole;phosphodiesterase;metabolic stability;pulmonary fibrosis;molecular docking
研究领域:
药理学
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药物化学
·
呼吸系统疾病
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jianhui Feng,Wenhao Cao,Bo Xu,Zhenhua Wang
Erectile dysfunction (ED) is a male sexual disorder mainly caused by a reduction in the cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by phosphodiesterase type-5 (PDE-5). Oyster protein (OP) and its hydrolysates have been used for centuries to address male erectile dysfunction, however the mechanisms and evidence supporting their efficacy remain unclear. In this study, OP was hydrolyzed using trypsin to produce peptides that inhibit PDE-5. Following separation by ultrafiltration and Sephadex G-25, a total of 3202 peptides were identified. Virtual screening and molecular docking were employed to identify PDE-5 inhibitory peptides and elucidate their interaction mechanisms with PDE-5. Five peptides with the sequences FLF, LMF, LLW, FGPF, and IPW demonstrated strong interactions with PED5. The results indicated that the key binding sites critical for docking included Phe820, Gln817 and Val782 of the target receptor PED-5. The highest inhibition rate observed for FGPF was 94.6 %, while the inhibition rates for IPW and FLF were 89.0 % and 87.6 %, respectively. The lowest inhibition rate was recorded for LLW at 68 %. These findings suggest that these five peptides have the potential to serve as PDE-5 inhibitors in the health food industry and medicine.
研究领域:
药理学
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生物信息学
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食品科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jianle Zhou,Liang Li,Hailu Zhang,Jiangping Xu,Dandan Huang,Ningbo Gong,Weili Han,Xuemei Yang,Zhengzheng Zhou
Cocrystallization of chlorbipram (ChBP), a novel phosphodiesterase-4 (PDE) inhibitor with water insoluble property developed in our lab, was performed to improve the physicochemical properties and bioavailability in the present study. Three new cocrystals with fumaric aicd (FA), gentisic acid (GA) and salicylic acid (SA) as coformers were synthesized and fully characterized by using the combination of multi-techniques. The cocrystals are phase stable even under high humidity conditions. In vitro study indicates that the solubility of ChBP-GA and ChBP-SA cocrystals increase to 3724.4 ± 58.7, 2897.4 ± 81.9 μg/mL in comparison with ChBP (2561.3 ± 150.4 μg/mL), the intrinsic dissolution rates (IDRs) of ChBP-GA and ChBP-SA cocrystals (721.3 ± 8.0, 614.4 ± 13.2 μg/min/cm 2 ) are both higher than ChBP (537.9 ± 12.0 μg/min/cm 2 ). The blood concentration peak values of ChBP-GA and ChBP-SA cocrystals (165.8 ± 50.9, 105.3 ± 35.6 ng/mL) are both higher than ChBP (51.3 ± 15.1 ng/mL) in in vivo evaluation. It presents the same order in in vitro/vivo study: ChBP-GA > ChBP-SA > ChBP > ChBP-FA. ChBP-FA cocrystal presents a longer elimination half life ( t 1/2 = 10.0 ± 2.6 h), which makes it a potential candidate for prolonged controlled release formulation . ChBP-GA and ChBP-SA cocrystals both present enhanced solubility and bioavailability in comparison with ChBP, making them a better candidate for the solid dosage formulation development.
研究领域:
药学
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晶体学
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药物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 11
·5680
·
IF 5.924
Long Tang,Jianchun Jiang,Guoqiang Song,Yajing Wang,Ziheng Zhuang,Ying Tan,Yan Xia,Xianfeng Huang,Xiaoqing Feng
Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative1fwas found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.Keywords:alkoxylated 6H-benzo[c]chromen-6-one;phosphodiesterase II;inhibitors;biological activities
研究领域:
药理学
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有机化学
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神经科学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2025
·
IF 8
Langjie Ye,Guanyong Su
The current scope of environmental monitoring studies primarily focuses on organophosphate triesters (OPTEs), neglecting their potential transformation products, i.e. organophosphate diesters (OPDEs). Furthermore, there is a notable absence of comprehensive screening strategies for all potential OPDEs in environmental samples. Herein, we pioneered an effective and precise screening strategy, incorporating target, suspect, and functional group-dependent nontarget screening, founded on ultrahigh performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and this strategy was applied to analyze n = 74 sediment samples, comprising 23 surface sediment samples and 51 sediment core samples, collected from Taihu Lake in eastern China during 2019. Through this analysis, we successfully identified 29 OPDEs, marking the first documentation of their presence in this region. Additionally, our study yielded noteworthy insights: 1) most OPDEs exhibited no significant correlations with their parent compounds, indicating their intricate origins within Taihu Lake; 2) two newly identified substances, distearyl phosphate (DSP) and diheptadecyl phosphate (DHP), were widespread and likely introduced through various rivers, potentially originating from chemical industry facilities or manufacturers situated along the rivers in the Taihu Lake basin; 3) vertical analysis revealed the pervasive presence of long-chain alkyl OPDEs in sediment cores from Taihu Lake, consistent with their high hydrophobicity. Collectively, this study has introduced an effective screening strategy successfully applied to comprehensively assess OPDEs in Taihu Lake sediments. This methodology holds promising potential for extension to various other environmental matrices or samples.
研究领域:
环境监测
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分析化学
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环境科学
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质谱分析
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色谱分析
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 68
·41551-41559
·
IF 3.119
Jinyan Du,Shuangqing Qi,Juan Chen,Ying Yang,Tingting Fan,Ping Zhang,Shujuan Zhuo,Changqing Zhu
Ce-Doped carbon dots (CeCDs) were fabricated via a one-step hydrothermal carbonization using Ce(NO3)3·6H2O and EDTA·2H2O as precursors, and various experimental techniques were employed to characterize the morphology, structure and composition of the as-obtained CeCDs. Using the disodium salt of bis(4-nitrophenyl)phosphate (BNPP) as a DNA model substrate, mimetic phosphatase activity toward phosphate ester hydrolysis cleavage was investigated. It was found that similar to the catalytic character of the natural enzyme, CeCDs as a hydrolase mimic can exhibit a good catalytic activity for promoting BNPP hydrolysis, in which metal Ce(III) acts as a center for binding and activation of the metal-bound hydroxide complex as well as a source of nucleophilic metal hydroxides. Additionally, based on the Inner Filter Effect (IFE), fluorescence spectra can be used to monitor the hydrolysis of BNPP using CeCDs, which mimic phosphatase. Thus, the unique properties of the CeCD mimetic phosphatases as well as the IFE sensing strategy would provide an ideal platform to monitor the catalytic phosphate ester hydrolysis processes. Finally, to validate the availability of the established catalytic systems, the CeCDs were further applied for degradation of organophosphorus pesticide chlorpyrifos. The degradation efficiency was estimated to be a satisfactory value of 74.50%, exhibiting a potential application prospect for treatment of the pollutants in the soil and water.
研究领域:
材料科学
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生物化学
·
环境科学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2020
·
IF 3.263
Minchi Liu,Wenjun Qian,Selvaraj Subramaniyam,Shuang Liu,Wenkuan Xin
Bitter taste receptors (Tas2rs) initiate a bitter taste signaling involving the activation of taste-specific G protein gustducin and phosphodiesterases (PDEs); it leads to the decrease of cytosolic level of cyclic adenosine monophosphate (cAMP) in taste cells. Recent studies have identified the expression of Tas2rs in a variety of non-lingual tissues including vascular smooth muscle (VSM), pulmonary smooth muscle and airway smooth muscle. The current study aims to determine the expression of Tas2rs and gustducin in rat aortic smooth muscle tissue and to investigate the effect of Tas2rs agonist denatonium on the tone of isolated denuded aorta rings. Here we reported the expression of six subtypes of Tas2r mRNA and the taste receptor-associated G proteins in endothelium-denuded aorta. Immunostaining experiments showed that the protein of gustducin expressed in vascular smooth muscle cells (VSMCs). Furthermore, denatonium increased the tone of freshly isolated denuded aorta rings in a concentration-dependent manner, and the potentiation effect of denatonium was blocked by a Tas2rs antagonist adenosine 5′-monophosphate (5′-AMP), by the cAMP-hydrolyzing PDE inhibitors , and by a cAMP-synthesizing enzyme activator forskolin , respectively. The blockade of G βγ signaling did not have a negative impact on the denatonium-induced tonic contractions. These findings suggested that the functional Tas2rs and gustducin are expressed in rat aortic smooth muscle and that denatonium might increase the smooth muscle tone through a Tas2rs signaling pathway involving the activation of PDEs.
研究领域:
药理学
·
生理学
·
心血管研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Bei Zhang,Zhong-Kai Zou,Jian-Fan Cai,Wen-Ming Tan,Jun-Wei Chen,Wei-En Li,Jing-Nan Liang,Wei-Pei Wu,Gang Wang,Xiao-Hong Ruan,Pei-Liang Zhao
Phosphodiesterase 5 (PDE5) is a cGMP-specific hydrolytic enzyme and widely distributed in versatile tissues. PDE5 has been identified as a valid therapeutic target for treating erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, a hit-to-lead structural optimizations were performed on the PDE1 inhibitor 10c, leading to compound 14b possessing great potency against PDE5A (IC50 = 3 nM) with high selectivity over PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11 by more than 1125-fold, and remarkable safety properties. Furthermore, oral administration of 14b (5.0 mg/kg) exerted much better pharmacodynamics effects on both mPAP (mean pulmonary artery pressure) and RVHI (index of right ventricle hypertrophy) than sildenafil citrate (10.0 mg/kg) in a monocrotaline-induced PAH rat model. Overall, these results proposed a novel highly selective PDE5 inhibitor 14b which could serve as a potential candidate for treatment of PAH.
研究领域:
药理学
·
心血管疾病研究
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DOI
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2023
·
IF 1.4
Hecheng Wang,Long Tang,Wanhui Di,Feng Yan,Xianfeng Huang,Xiaoqing Feng,Guoqiang Song
Urolithins are the gut microbiota metabolites of ellagitannins which are found in natural plants such as pomegranate, strawberry, and raspberry, and in nuts. Recently, several reports have clarified the underlying mechanism of urolithins in central nervous system inflammation. Therefore, urolithins have become potential therapeutic drug candidate molecules for central nervous system diseases. Derivatives 1–1d, 1–1f, 3–2a, and 3–2b of urolithin A, urolithin B, and methoxyurolithin A were found to have had significant inhibitory activity against phosphodiesterase II with IC50 values of 35.42, 39.96, 25.58, and 13.84 μM, respectively. Herein, we report the design and synthesis of urolithin derivatives along with a biological evaluation of their activity against phosphodiesterase II.
研究领域:
药物化学
·
神经科学
·
生物合成
✓ 已验证
DOI
高影响因子
Foods
·
2023
·Vol. 12
·期 17
·3236
·
IF 5.2
Qianqian Huang,Haiying Wu,Xiaoming Qin
Pfaffia glomerataextract (PGE) has a variety of biological activities. However, its ameliorative effect on and exact working mechanism in male sexual dysfunction are still poorly understood. This study aims to evaluate the ameliorative effect of PGE on paroxetine (PRX)-induced sexual dysfunction in male mice and uses molecular docking technology to investigate its underlying mechanism. In this work, PRX-induced sexual dysfunction was caused and PGE was gavaged in mice for 28 days. The results show that PGE significantly improved the sexual performance of mice and reduced the damage to testicular tissues. Further studies showed that PGE restored serum sex hormones to normal levels and increased nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels as well as nitric oxide synthase (NOS) activity in penile tissues, while also decreasing phosphodiesterase-5 (PDE-5) activity, thereby maintaining normal penile erection in mice. In addition, PGE improved the activities of enzymes (LDH, ACP, and ALP) related to energy metabolism in the testis and significantly increased sperm count and viability in mice. Furthermore, the molecular docking results show that all eight compounds in PGE could form a stable complex with PDE-5 and inhibit the activity of PDE-5. In conclusion, PGE had an ameliorative effect on PRX-induced sexual dysfunction, suggesting that PGE has a potential protective effect on male sexual health.Keywords:Pfaffia glomerata;extract;sexual function;molecular docking;paroxetine
研究领域:
药理学
·
性健康
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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