含有O-基-劳松与2-基基-β-环氧德克斯特林的复合物:制备,物理特征,抗寄生虫和抗真菌活性
Caroline Deckmann Nicoletti1, Raíssa Maria Dos Santos Galvão2, Marcella de Sá Haddad Queiroz1
1Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, Universidade Federal Fluminense, 24241-000, Niterói, RJ, Brazil.
Journal of bioenergetics and biomembranes
|July 13, 2023
概括
将O-allyl-lawsone (OAL) 封装在2-hydroxypropyl-β-cyclodextrin (OAL MKN) 中可以增强其抗寄生虫和抗真菌活性. 这种OAL MKN配方显示出对Trypanosoma cruzi和Sporothrix酵母的有效性和选择性增加.
科学领域:
- 药用化学 医学化学
- 寄生虫学的寄生虫学
- 菌类学 菌类学是指菌类学.
背景情况:
- 纳夫托基诺具有显著的抗微生物特性.
- --松 (O-allyl-lawsone,简称OAL) 是一种纳夫托基,具有潜在的治疗应用.
- 寄生虫和真菌感染仍然是一个全球性的健康问题.
研究的目的:
- 评估O-allyl-lawsone (OAL) 和其封装形式OAL MKN.的抗寄生虫和抗真菌活性.
- 评估OAL MKN对Trypanosoma cruzi和Sporothrix物种的疗效. 为了评估OAL MKN对Trypanosoma cruzi和Sporothrix物种的疗效.
- 为了确定OAL和OAL MKN的细胞毒性和选择性.
主要方法:
- 合成和OAL和OAL MKN的物理化学表征.
- 在体外对Trypanosoma cruzi epimastigotes和trypomastigotes的抗寄生虫活性进行了评估.
- 在体外评估抗真菌活性对抗Sporothrix brasiliensis和Sporothrix schenckii.
- 用哺乳动物细胞进行细胞毒性测试.
主要成果:
- 与自由的OAL相比,OAL MKN对T. cruzi (0.5μM) 的IC50值明显较低.
- 在OAL MKN中,针对T. cruzi. 的选择性指数提高了 (比benznidazole高240倍).
- OAL和OAL MKN都抑制了Sporothrix物种的生长,OAL MKN表现出更好的选择性.
- OAL MKN对哺乳动物细胞的毒性较低.
结论:
- 将OAL封装在2-propyl-β-cyclodextrin (OAL MKN) 中可以增强其抗寄生虫和抗真菌特性.
- OAL MKN 对T. cruzi trypomastigotes和Sporothrix酵母具有更好的疗效和选择性.
- OAL MKN 纳入综合体对开发被忽视的寄生虫和真菌疾病的新疗法充满希望.
相关概念视频
Preparation of Diols and Pinacol Rearrangement
Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
π Molecular Orbitals of the Allyl Cation and Anion
An allyl group is a three-carbon conjugated system where the sp³-hybridized allylic carbon is bonded to a CH=CH2 group via a single bond. Allyl anions can be obtained by treating propene with a strong base that can deprotonate methyl groups. Allyl cations are formed as intermediates during substitution reactions involving allylic halides. In both cases, the hybridization of the allylic carbon changes from sp3 to sp2, giving rise to a carbon chain with three sp2-hybridized carbons, each with an...
Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
Candidiasis
Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Antifungal Agents
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...


