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叶绿素a向二氢卟吩e6衍生物的转化及其若干应用。

Transformation Chlorophyll a of to Chlorin e6 Derivatives and Several Applications.

作者信息

Bui Hoa Thi Hai, Pham Tam Thi, Nguyen Hien Thi Thu, Do Trung Minh, Nga Vu Thi, Bac Nguyen Duy, Huyen Vu Thi Bich, Le Hai Minh, Tran Quang Canh

机构信息

Hanoi Open University, Hanoi, Vietnam.

Vietnam Military Medical University, Hanoi, Vietnam.

出版信息

Open Access Maced J Med Sci. 2019 Dec 20;7(24):4372-4377. doi: 10.3889/oamjms.2019.838. eCollection 2019 Dec 30.

Abstract

BACKGROUND

Spirulina platensis contains a large amount of chlorophylls, chlorophyll a, that are starting materials to synthesize functionalized chlorins. Chlorin e6 (Ce6) as well as its derivatives are second generation sensitizers using in photodynamic therapy (PDT) of various cancers. In this study, we transfer chlorophyll a of S. platensis to Ce6 derivatives and determine their several applications.

AIM

We aimed to evaluate the effects of Ce6 derivatives to treat cancer cells.

METHODS

Ce6 trimethylester was created from methyl pheophorbide a2 in S. platensis provided by the Hidumi Company, Nghe An province, Viet Nam. Hela cells were incubated with Ce6 trimethylester and the irradiated with the diode laser dose of 1.2 J/cm/min through the system of filters £ 650 nm. MTT assay and clonogenic assay were used to determine survival rate and cloning efficiency of cells. Antimicrobial effect of Ce6 trimethylester with halogen light were studied with Propionibacterium acnes VTCC 0218 and Staphylococcus aureus VTCC 0173.

RESULTS

From dry biomass (700 g) of S. platensis, after extracting chlorophyll a and methanolysis, 4.2 g of methyl pheophorbide a was obtained. The reaction to give Ce6 trimethylester with 82% yield was performed with potassium hydroxide (KOH) in MeOH/THF/CHCl3. After irradiation with a 650 nm laser at 1.2 J, the cell viability in all samples decreased with Ce6 trimethylester treatment, the survival declining trend of Hela cells treated with Ce6 trimethylester were proportional when concentration of Ce6 trimethylester increased. The rate of colony formation was declined as the concentration of Ce6 trimethylester treated was increased. The growth of both S. aureus and P. acnes can be inactivated by Ce6 trimethylester PDT. The MIC99 value against P. acnes VTCC 0218 and S. aureus VTCC 0173 of Ce6 trimethylester with halogen light was 1.25 μg/ml.

CONCLUSION

The Ce6 trimethylester from S. platensis cultivated in Viet Nam could be used as a potential photosentizer for photodynamic therapy for treatment of cancer and acne.

摘要

背景

钝顶螺旋藻含有大量叶绿素,即叶绿素a,它们是合成功能化二氢卟吩的起始原料。二氢卟吩e6(Ce6)及其衍生物是用于各种癌症光动力疗法(PDT)的第二代光敏剂。在本研究中,我们将钝顶螺旋藻的叶绿素a转化为Ce6衍生物,并确定其多种应用。

目的

我们旨在评估Ce6衍生物对癌细胞的治疗效果。

方法

Ce6三甲酯由越南义安省希杜米公司提供的钝顶螺旋藻中的脱镁叶绿酸a2甲酯制备而成。将HeLa细胞与Ce6三甲酯孵育,然后通过650 nm的滤光片系统用二极管激光以1.2 J/cm/min的剂量照射。采用MTT法和克隆形成试验来确定细胞的存活率和克隆效率。用痤疮丙酸杆菌VTCC 0218和金黄色葡萄球菌VTCC 0173研究Ce6三甲酯在卤素光下的抗菌效果。

结果

从700 g钝顶螺旋藻的干生物量中,提取叶绿素a并进行甲醇解后,得到4.2 g脱镁叶绿酸a甲酯。在MeOH/THF/CHCl3中用氢氧化钾(KOH)进行反应,以82%的产率得到Ce6三甲酯。用650 nm激光以1.2 J照射后,所有样品中经Ce6三甲酯处理的细胞活力均下降,随着Ce6三甲酯浓度的增加,HeLa细胞经Ce6三甲酯处理后的存活下降趋势呈正比。随着Ce6三甲酯处理浓度的增加,集落形成率下降。Ce6三甲酯光动力疗法可使金黄色葡萄球菌和痤疮丙酸杆菌的生长失活。Ce6三甲酯在卤素光下对痤疮丙酸杆菌VTCC 0218和金黄色葡萄球菌VTCC 0173的MIC99值为1.25 μg/ml。

结论

越南种植的钝顶螺旋藻中的Ce6三甲酯可作为一种潜在的光敏剂用于癌症和痤疮的光动力治疗。

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