MEDICINAL CHEMISTRY RESEARCH
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2021
·Vol. 30
·期 12
·2228-2239
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IF 1.965
Shang Fan-Fan,Wang Mei-Yuan,Ai Jiang-Ping,Shen Qing-Kun,Guo Hong-Yan,Jin Chun-Mei,Chen Fen-Er,Quan Zhe-Shan,Jin Lili,Zhang Changhao
Nineteen mycophenolic acid (MPA) derivatives were designed and synthesized, and their anti- Toxoplasma activity evaluated for the first time. Among them, N -propylimidazole-modified compound E5 demonstrated the strongest activity, and the IC 50 against HFF-1 (Human Foreskin Fibroblasts-1) cells following infection with T. gondii is 80.9 μM (MPA-211.5 μM) and its selectivity index is 2.2 (MPA-1.2). In vivo experiments, E5 can significantly inhibit the proliferation of tachyzoites in the abdominal cavity of mice acutely infected with T. gondii (inhibition rates 46.7%), and this inhibitory effect was greater than that of spiramycin (inhibition rates 31.3%) and MPA (inhibition rates 15.9%), this indicated that E5 had significant protective effects on the host during acute Toxoplasma infection. In addition, E5 can reduce the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of infected mice, significantly increase the level of glutathione (GSH) in the liver, and significantly reduce the level of malondialdehyde (MDA), indicating that it has a hepatoprotective effect against T. gondii infection. Similarly, E5 can relieve hepatomegaly and splenomegaly induced by acute Toxoplasma infection. Spiramycin aggravated appetite loss in infected mice, while E5 did not. In summary, the results indicated that E5 has potential as a candidate anti- T. gondii drug.
研究领域:
药理学
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寄生虫学
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药物化学
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DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 21
·5024
·
IF 4.2
Jieqiong Wang,Weifeng Yan,Xu Cheng,Yonggang Tong,Sihong Wang,Chunmei Jin
Toxoplasmosis, a zoonotic infection caused byToxoplasma gondii(T. gondii), poses a significant risk to human health and public safety. Despite the availability of clinical treatments, none effectively mitigate the intestinal barrier damage, which is the primary defense againstT. gondiiinvasion. This study introduced aldehyde groups into the indole scaffold of a peptide-like structure to investigate the protective effects of these indole aldehyde derivatives on the intestinal barrier in mice with acuteT. gondiiinfection. This approach leveraged the propensity of peptides and aldehyde groups to form hydrogen bonds. We synthesized a range of indole derivatives using the Vilsmeier–Haack reaction and evaluated their intestinal barrier protective effects both in vitro and in vivo. Our findings revealed that indole derivativesA1(1-Formyl-1H-indole-3-acetonitrile),A3(Indole-3-carboxaldehyde),A5(2-Chloro-1H-indole-3-carboxaldehyde),A8(1-Methyl-indole-3-carboxaldehyde), andA9(1-Methyl-2-phenyl-1H-indole-3-carboxaldehyde) demonstrated a higher selectivity index compared to the positive control, spiramycin. These derivatives enhanced gastrointestinal motility, increased glutathione (GSH) levels in the small intestine, and reduced malondialdehyde (MDA) and nitric oxide (NO) levels in the small intestine tissue and diamine oxidase (DAO) and NO levels in the serum of infected mice. Notably,A3exhibited comparable anti-T. gondiitachyzoites activity in the peritoneal cavity. Molecular docking studies indicated that the aldehyde group on the indole scaffold not only formed a hydrogen bond with NTPase-II but also interacted with TgCDPK1 through hydrogen bonding. Among the derivatives,A3showed promising intestinal barrier protective effects in mice with acuteT. gondiiinfection. This research suggests that indole derivatives could serve as a potential therapeutic strategy for intestinal diseases induced byT. gondii,offering a novel direction for treating intestinal barrier damage and providing valuable insights for the chemical modification of drugs targetingT. gondii. Furthermore, it contributes to the advancement of therapeutic approaches for toxoplasmosis.
研究领域:
药理学
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寄生虫学
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分子生物学
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传染病学
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药物发现
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Wenzhang Jin,Shuqi Shen,Xiaoniuyue Xu,Xueting Xie,Xingjian Zhou,Xiang Su,Lina Wu,Shunfu Wang,Lijiang Zhang,Bicheng Chen,Fajing Yang
The current wound healing process faces numerous challenges such as bacterial infection, inflammation and oxidative stress. However, wound dressings used to promote wound healing, are not well suited to meet the clinical needs. Hyaluronic acid (HA) not only has excellent water absorption and good biocompatibility but facilitates cell function and tissue regeneration. Dopamine, on the other hand, increases the overall viscosity of the hydrogel and possesses antioxidant property. Furthermore, chitosan exhibits outstanding performance in antimicrobial, anti-inflammatory and antioxidant activities. Basic fibroblast growth factor (bFGF) is conducive to cell proliferation and migration, vascular regeneration and wound healing. Hence, we designed an all-in-one hydrogel patch containing dopamine and chitosan framed by hyaluronic acid (HDC) with sprayed gelatin methacryloyl (GelMA) microspheres loaded with bFGF (HDC-bFGF). The hydrogel patch exhibits excellent adhesive, anti-inflammatory, antioxidant and antibacterial properties. In vitro experiments, the HDC-bFGF hydrogel patch not only showed significant inhibitory effect on RAW cell inflammation and Staphylococcus aureus (S. aureus) growth but also effectively scavenged free radicals, in addition to promoting the migration of 3 T3 cells. In the mice acute infected wound model, the HDC-bFGF hydrogel patch adhered to the wound surface greatly accelerated the healing process via its anti-inflammatory and antioxidant activities, bacterial inhibition and pro-vascularization effects. Therefore, the multifunctional HDC-bFGF hydrogel patch holds great promise for clinical application.
研究领域:
生物医学工程
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伤口愈合
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药学
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生物材料
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DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Jie Hu,Rui Chen,Zhenglin Li,Fenzan Wu,Yanhong Yang,Yu Yang,Xiaokun Li,Jian Xiao
The management and treatment of acute infected wounds, which are characterized by bacterial infections and excessive amount of reactive oxygen species, remains a major challenge in clinic. Herein, a facile and universal approach for constructing polyphenol-coordinated supramolecular hydrogel is developed for acute infected wound treatment. The hydrogels are mainly crosslinked via two types of noncovalent bond associations, i.e., the intermolecular hydrogen bonding between polyphenols and poly-vinylpyrrolidone/basic fibroblast growth factor (bFGF) components, and the metal-phenolic hydroxyl coordination interactions. Taking tannic acid (TA) as a model polyphenol for biomedical application, TA-based hydrogel (TPFe or TPFe/bFGF hydrogel) is demonstrated to possess multifunctional features, including: 1) potent adhesive capacity for adhesion to the wounds or cementing two separated tissues together; 2) hemostatic property against rats’ tail cut, liver incision, and heart hole bleeding within a few minutes; 3) antioxidant ability for DPPH and ABTS radical scavenging activities; 4) antibacterial activity especially for Staphylococcus aureus ; 5) accelerated endothelial cells migration/proliferation and angiogenesis, which are attributed to bFGF delivery from the hydrogel. In vitro / vivo experimental results show that TPFe hydrogel has excellent biocompatibility, and faster healing rates are observed in animal tests whether with a full-thickness skin defect model or a bacterial-infected wound model. Hence, our work reveals that such supramolecular hydrogel with multiple functions may be well adaptive to the different stages of wound repair process, and thus highlights its great prospect as a promising “One-Stop-Shop” strategy for acute infected wound treatment.
研究领域:
材料科学
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生物材料
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伤口愈合
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）