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三萜类衍生物作为新型抗生物膜药物的相关支架。

Triterpene Derivatives as Relevant Scaffold for New Antibiofilm Drugs.

机构信息

Laboratório de Fitoquímica e Síntese Orgânica, Faculdade de Farmácia, Universidade Federaldo Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90610-000, Brasil.

Laboratório de Biofilmes e Diversidade, Faculdade de Farmácia and Centro de Biotecnologia, UniversidadeFederal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 91501-970, Brasil.

出版信息

Biomolecules. 2019 Feb 11;9(2):58. doi: 10.3390/biom9020058.

Abstract

New medicines for the treatment of bacterial biofilm formation are required. For thisreason, this study shows the in vitro activity of betulinic acid (BA), ursolic acid (UA) and their twentyderivatives against planktonic and biofilm cells (gram-positive bacterial pathogens: Enterococcusfaecalis, and ). We evaluated the antibiofilm activity(through the crystal violet method), as well as the antibacterial activity via absorbance (OD) atconcentrations of 5, 25 and 100 μM. Likewise, the cytotoxicity of all compounds was evaluated on akidney African green monkey (VERO) cell line at the same concentration, by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) methodology. We verified for the first timewhether different groups at carbon 3 (C-3) of triterpenes may interfere in the antibiofilm activity withminimal or no antibacterial effect. After the screening of 22 compounds at three distinctconcentrations, we found antibiofilm activity for eight distinct derivatives without antibiotic effect.In particular, the derivative 2f, with an isopentanoyl ester at position C-3, was an antibiofilm activityagainst S. aureus without any effect upon mammalian cells.

摘要

需要新的药物来治疗细菌生物膜的形成。因此,本研究显示了白桦脂酸(BA)、熊果酸(UA)及其二十种衍生物对浮游和生物膜细胞(革兰氏阳性细菌病原体:粪肠球菌和金黄色葡萄球菌)的体外活性。我们评估了抗生物膜活性(通过结晶紫法),以及在 5、25 和 100 μM 浓度下通过吸光度(OD)评估的抗菌活性。同样,通过 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物)方法,在相同浓度下,在肾脏非洲绿猴(VERO)细胞系上评估了所有化合物的细胞毒性。我们首次验证了萜类化合物在碳 3(C-3)上的不同基团是否可能通过最小或没有抗菌作用来干扰抗生物膜活性。在对三种不同浓度的 22 种化合物进行筛选后,我们发现了八种不同的衍生物具有抗生物膜活性而没有抗生素作用。特别是,在 C-3 位具有异戊酰酯的衍生物 2f 对金黄色葡萄球菌具有抗生物膜活性,而对哺乳动物细胞没有任何影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef76/6406419/c7d4ab3920a4/biomolecules-09-00058-g001.jpg

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