ARCHIV DER PHARMAZIE
·
2023
·Vol. 356
·期 8
·2300110
·
IF 5.1
Jun-Da Qi,Yu-Qing Meng,Jingxin Sun,Wan-Xin Li,Hou-Xiang Zhai,Changhao Zhang,Jishan Quan,Cheng-Hua Jin
Four series of novel pyrazole derivatives (compounds 17a – m, 18a – m, 19a – g , and 20a – g ) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds ( 17a – m, 18k – m , and 19b – g ) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.
研究领域:
药物化学
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药理学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Danmei Tian,Fangfang Wang,Menglong Duan,Lingyun Cao,Youwei Zhang,Xinsheng Yao,Jinshan Tang
Seven new coumarin analogues (1, 2, and 4–8), together with ten known analogues (3, 9–17), were isolated from the air-dried pericarp of Citrus grandis. The structures of these compounds were determined by HR-ESI-MS, UV/vis, and 1D- and 2D-NMR spectra. Meanwhile, the hepatoprotective activities of all these coumarins were evaluated by MTT assays using the d-galactosamine-induced LO2 cell injury model. The results show that compounds 3 and 4 exhibited the strongest hepatoprotective activities. Moreover, compounds 3 and 4 suppressed increases in the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in d-galactosamine-treated LO2 cells, further confirming the hepatoprotective effects of these compounds. Mechanistically, compounds 3 and 4 increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the level of malondialdehyde (MDA) in injured LO2 cells induced by d-galactosamine. These findings shed light on a better understanding of the hepatoprotective effect of Citrus grandis, providing novel insights into the development of coumarin-based hepatoprotective drugs in the future.
研究领域:
药理学
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天然产物化学
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肝病学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Shuwei Ke,Siyu Zhang,Dongsheng Liu,Tengjiao Zhao,Xiayan Lou,Sunying Cheng,Tingheng Zhu,Hanbing Li
Ectopic olfactory receptors, such as OR1A1, are involved in the regulation of lipid metabolism homeostasis. In this study, we investigated the effects of three monoterpenes, (+)-limonene, (−)-carvone and thymol, upon hepatic lipid deposition. Oral administration of (+)-limonene, (−)-carvone and thymol for 8 weeks in high-fat-diet (HFD)-fed mice significantly lowered the levels of fasting blood glucose, improved glucose intolerance, serum lipid parameters, adiposity, and hepatic steatosis. In LO2 cells, (+)-limonene, (−)-carvone and thymol increased the cyclic adenosine monophosphate (cAMP), induced protein kinase A (PKA) activity and phosphorylation of AMPK, downregulated the expression of SREBP-1 and FASN, and eventually led to a reduction in hepatic lipid deposition. Meanwhile, these beneficial effects in cultured LO2 cells were negated by OR1A1 knockdown and the adenylyl cyclase inhibitor SQ22536, respectively, indicating that they can ameliorate disorders of lipid metabolism through activating OR1A1 and subsequent AMPK/SREBP-1/FASN pathway, indicating OR1A1 as a potential target for counteracting hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
·
分子生物学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Miao Jiefei,Meng Chi,Wu Hongmei,Shan Wenpei,Wang Haoran,Ling Changchun,Zhang Jinlin,Yang Tao
A novel hybrid CHC was designed and synthesized by conjugating β-carboline with an important active fragment N-hydroxyacrylamide of histone deacetylase (HDAC) inhibitor by an amide linkage to enhance antitumor efficacy/potency or even block drug resistance. CHC displayed high antiproliferative effects against drug-sensitive SUMM-7721, Bel7402, Huh7, and HCT116 cells and drug-resistant Bel7402/5FU cells with IC50 values ranging from 1.84 to 3.27 μM, which were two-to four-fold lower than those of FDA-approved HDAC inhibitor SAHA. However, CHC had relatively weak effect on non-tumor hepatic LO2 cells. Furthermore, CHC exhibited selective HDAC1/6 inhibitory effects and simultaneously augmented the acetylated histone H3/H4 and α-tubulin, which may make a great contribution to their antiproliferative effects. In addition, CHC also electrostatically interacted with CT-DNA, exerted remarkable cellular apoptosis by regulating the expression of apoptosis-related proteins and DNA damage proteins in Bel7402/5FU cells, and significantly accumulated cancer cells at the G2/M phase of the cell cycle by suppressing CDK1 and cyclin B protein with greater potency than SAHA-treated groups. Finally, CHC displayed strong inhibitory potency to drug-resistant hepatic tumors in mice. Our designed and synthetic hybrid CHC could be further developed as a significant and selective anticancer agent to potentially treat drug-resistant hepatocellular carcinoma.
研究领域:
药理学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jin Li,Hui Wang,Jingbo Xu,Shengyue Wu,Mengmeng Han,Jianfei Li,Qianqian Wang,Zhiming Ge
Discoid-reconstituted high-density lipoprotein (d-rHDL) is advantageous for tumor-targeted drug delivery due to its small size, long circulation, and efficient internalization into cancer cells. Nevertheless, an allosteric reaction catalyzed by serum lecithin-cholesterol acyltransferase (LCAT) may cause drug leakage from d-rHDL and reduce its targeting efficiency. Conversely, similar “structural weakening” catalyzed by acyl-coenzyme A-cholesterol acyltransferase (ACAT) inside tumor cells can stimulate precise intracellular drug release. Therefore, we synthesized and characterized a pH-sensitive n-butyraldehyde bi-cholesterol (BCC) to substitute for cholesterol in the d-rHDL particle, and bovine serum albumin (BSA) was used as the targeting agent. This dual pH- and ACAT-sensitive d-rHDL (d-d-rHDL) was small with a disk-like appearance. Morphological transformation observation, in vitro release assays, and differences in internalization upon LCAT treatment confirmed that BCC effectively inhibited the remodeling behavior and enhanced the tumor-targeting efficiency. The accumulation of d-d-rHDL in HepG2 cells was significantly higher than that in LO2 cells, and accumulation was inhibited by free BSA. The pH sensitivity was verified, and d-d-rHDL achieved efficient drug release in vitro and inside tumor cells after exposure to acidic conditions and ACAT. Confocal laser scanning microscopy demonstrated that d-d-rHDL escaped from lysosomes and became distributed evenly throughout cells. Moreover, in vivo imaging assays in a tumor-bearing mouse model demonstrated tumor-targeting properties of d-d-rHDL, and paclitaxel-loaded d-d-rHDL showed strong anticancer activity in these mice. This dual-sensitive d-d-rHDL thus combines structural stability in plasma and an intracellular pH/ACAT-triggered drug release to facilitate inhibition of tumor growth.
研究领域:
药学
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癌症研究
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药物递送系统
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Xuewei Jia,Yanchao Yao,Guofeng Yu,Lili Qu,Tianxiao Li,Zhenjie Li,Chunping Xu
Polysaccharides are ideal green synthetic raw materials to improve the biocompatibility of metal nanoparticles. However, polysaccharides generally have weak reducibilities, being challenging supports for the direct preparation of Ag nanoparticles. In this work, gold nanoclusters were prepared using a triple helix glucan (Lentinan) via microwave-assisted synthesis and subsequently employed as seeds for the synthesis of a series of Ag-Au alloy nanoparticles (Ag-AuNPs). The results showed that gold nanoclusters can remarkably speed up the preparation of Ag-AuNPs without the addition of any other chemicals. The particle size of Ag-AuNPs increased at increasing Ag contents in the alloy. Results of UV–vis, transmission electron microscope (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) suggested that Ag + was quickly reduced to irregular silver nanoparticles (with gold nanoparticles as seeds), then gradually form more regular nano-alloys. Additionally, X-ray diffraction (XRD) and zeta potential results suggested that Ag-AuNPs could entrap the hydrophobic cavity of triple helix polysaccharides during the renaturation process. The nanocomposites exhibited good antifungal activity and low cytotoxicity to RAW264.7, Hela and LO2 cell lines in vitro .
研究领域:
纳米技术
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材料科学
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生物技术
·
药学
✓ 已验证
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）