Synthesis and Investigation of Photophysical and Biological Properties of Novel S-Containing Bacteriopurpurinimides,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis and Investigation of Photophysical and Biological Properties of Novel S-Containing Bacteriopurpurinimides
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-12-18 00:00:00 , DOI: 10.1021/acs.jmedchem.7b00577
Andrey F. Mironov ₁ , Mikhail A. Grin ₁ , Ivan V. Pantushenko ₁ , Petr V. Ostroverkhov ₁ , Yan A. Ivanenkov _{2,

3} , Gleb I. Filkov ₄ , Ekaterina A. Plotnikova ₅ , Tatyana A. Karmakova ₅ , Anna V. Starovoitova ₆ , Nelli.V. Burmistrova ₆ , Vadim V. Yuzhakov ₆ , Yuri S. Romanko ₆ , Maxim A. Abakumov _{7,

8} , Anastasiya A. Ignatova _{9,

10} , Alexey V. Feofanov _{9,

10} , Mikhail A. Kaplan ₆ , Raisa I. Yakubovskaya ₅ , Anatoliy A. Tsigankov ₁₁ , Alexander G. Majouga _{2,

8}

Affiliation

Moscow Technological University, 86 Vernadsky Avenue, Moscow 119571, Russia
Chemistry Department, Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russia
Institute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Ufa, Bashkortostan, Russian Federation
Moscow Institute of Physics and Technology (MIPT), 9 Institutskiy Per., Dolgoprudny, Moscow Region 141700, Russia
Branch, National Medical Radiology Research Center, P. A. Herzen Moscow Oncology Research Institute, 3 2nd Botkinskiy Proezd, Moscow 125284, Russia
A. Tsyb Medical Radiological Research Centre (A. Tsyb MRRC), 10 Zhukov Street, Obninsk, Kaluga Region, 249031, Russia
Pirogov Russian National Research Medical University (RNRMU), 1 Ostrovitianov Street, Moscow 117997, Russia
National University of Science and Technology MISiS, Leninsky Prospect 4, Moscow 119049, Russia
Shemyakin−Ovchinnikov Institute of Bioorganic Chemistry, RAS, GSP-7, Ulitsa Miklukho-Maklaya 16/10, Moscow 117997, Russia
Biology Faculty, Lomonosov Moscow State University, Leninskie Gory 1/70, Moscow 119992, Russia
Institute of Fundamental Problems of Biology, Russian Academy of Sciences Pushino, Moscow Region 142290, Russia

Novel hybrid molecule containing 2-mercaptoethylamine was synthesized starting from O-propyloxime-N-propoxy bacteriopurpurinimide (dipropoxy-BPI), which was readily oxidized in oxygen atmosphere yielding the corresponding disulfide analogue (disulfide-BPI). Spectral, photophysical, photodynamic, and biological properties of compound were properly evaluated. Compounds bearing disulfide moiety can directly interact with glutathione (GSH), thereby reducing its intracellular concentration. Indeed, mice sarcoma S37 cell line was treated in vitro with disulfide-BPI, yielding a CC₅₀ value of 0.05 ± 0.005 μM. A relatively high level of singlet oxygen was detected. It was demonstrated (by fluorescence) that the PS was rapidly accumulated in a cancer nest (S37) at a relatively high level after 2 h upon intravenous administration. After 24 h, no traces of the molecule were detected in the tumor mass. Moreover, high photodynamic efficiency was demonstrated at doses of 150–300 J/cm² against two different in vivo tumor models, achieving 100% regression of cancer growth.

中文翻译：

合成及光物理和生物学特性的研究小号含Bacteriopurpurinimides

由O-丙基肟-N-丙氧基细菌紫嘌呤酰亚胺（dipropoxy-BPI）合成了含有2-巯基乙胺的新型杂化分子，该分子在氧气气氛中容易被氧化，生成相应的二硫化物类似物（disulfide-BPI）。正确评估了化合物的光谱，光物理，光动力学和生物学特性。带有二硫键部分的化合物可以直接与谷胱甘肽（GSH）相互作用，从而降低其细胞内浓度。确实，小鼠肉瘤S37细胞系在体外用二硫键BPI处理，产生的CC ₅₀值为0.05±0.005μM。检测到相对较高的单线态氧。（通过荧光证明）在静脉内给药2小时后，PS以相对较高的水平迅速聚集在癌巢（S37）中。24小时后，在肿瘤块中未检测到该分子的痕迹。此外，在150-300 J / cm ^2的剂量下，针对两种不同的体内肿瘤模型显示出较高的光动力学效率，从而实现了100％的癌症生长消退。

更新日期：2017-12-18

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11