Synthesis, Cytotoxic Activity Evaluation and Quantitative Structure-ActivityAnalysis of Substituted 5,8-Dihydroxy-1,4-naphthoquinones and Their O- and S-Glycoside Derivatives Tested against Neuro-2a Cancer Cells

被引：8

作者：

Polonik, Sergey ^{[1
]}

Likhatskaya, Galina ^{[1
]}

Sabutski, Yuri ^{[1
]}

Pelageev, Dmitry ^{[1
,2
]}

Denisenko, Vladimir ^{[1
]}

Pislyagin, Evgeny ^{[1
]}

Chingizova, Ekaterina ^{[1
]}

Menchinskaya, Ekaterina ^{[1
]}

Aminin, Dmitry ^{[1
,3
]}

机构：

[1] Russian Acad Sci, GB Elyakov Pacific Inst Bioorgan Chem, Far Eastern Branch, Prospekt 100 Let Vladivostoku,159, Vladivostok 690022, Russia

[2] Far Eastern Fed Univ, Sch Nat Sci, Sukhanova St 8, Vladivostok 690091, Russia

[3] Kaohsiung Med Univ, Dept Biomed Sci & Environm Biol, 100,Shih Chuan 1st Rd, Kaohsiung 80708, Taiwan

来源：

MARINE DRUGS | 2020年 / 18卷 / 12期

基金：

俄罗斯科学基金会;

关键词：

neuroblastoma Neuro-2a cells; 5; 8-dihydroxy-1; 4-naphthoquinone; O-glucoside; thiomethylglycoside; cytotoxic activity; QSAR; 1,4-NAPHTHOQUINONE DERIVATIVES; NAPHTHOQUINONE DERIVATIVES; ANTICANCER ACTIVITIES; BRAIN-TUMORS; ECHINOCHROME; ANTIBACTERIAL; STRATEGIES; APOPTOSIS;

D O I：

10.3390/md18120602

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on 6,7-substituted 2,5,8-trihydroxy-1,4-naphtoquinones (1,4-NQs) derived from sea urchins, five new acetyl-O-glucosides of NQs were prepared. A new method of conjugation of per-O-acetylated 1-mercaptosaccharides with 2-hydroxy-1,4-NQs through a methylene spacer was developed. Methylation of 2-hydroxy group of quinone core of acetylthiomethylglycosides by diazomethane and deacetylation of sugar moiety led to 28 new thiomethylglycosidesof 2-hydroxy- and 2-methoxy-1,4-NQs. The cytotoxic activity of starting 1,4-NQs (13 compounds) and their O- and S-glycoside derivatives (37 compounds) was determined by the MTT method against Neuro-2a mouse neuroblastoma cells. Cytotoxic compounds with EC50 = 2.7-87.0 mu M and nontoxic compounds with EC50 > 100 mu M were found. Acetylated O- and S-glycosides 1,4-NQs were the most potent, with EC50 = 2.7-16.4 mu M. Methylation of the 2-OH group innaphthoquinone core led to a sharp increase in the cytotoxic activity of acetylated thioglycosidesof NQs, which was partially retained for their deacetylated derivatives. Thiomethylglycosides of 2-hydroxy-1,4-NQs with OH and MeO groups in quinone core at positions 6 and 7, resprectively formed a nontoxic set of compounds with EC50 > 100 mu M. A quantitative structure-activity relationship (QSAR) model of cytotoxic activity of 22 1,4-NQ derivatives was constructed and tested. Descriptors related to the cytotoxic activity of new 1,4-NQ derivatives were determined. The QSAR model is good at predicting the activity of 1,4-NQ derivatives which are unused for QSAR models and nontoxic derivatives.

引用

页数：29