Synthesis and biological evaluation of Schizandrin derivatives as potential anti-cancer agents

被引：32

作者：

Amujuri, Devi ^{[1
]}

Siva, Bandi ^{[1
]}

Poornima, B. ^{[1
]}

Sirisha, Katukuri ^{[2
]}

Sarma, A. V. S. ^{[2
]}

Nayak, V. Lakshma ^{[3
]}

Tiwari, Ashok K. ^{[3
]}

Purushotham, U. ^{[4
]}

Babu, K. Suresh ^{[1
]}

机构：

[1] CSIR Indian Inst Chem Technol, Div Nat Prod Chem, Hyderabad 500007, Andhra Pradesh, India

[2] CSIR Indian Inst Chem Technol, Ctr NMR & Struct Chem, Uppal Rd, Hyderabad 500607, Andhra Pradesh, India

[3] CSIR Indian Inst Chem Technol, Div Med Chem & Biotechnol, Hyderabad 500007, Andhra Pradesh, India

[4] KL Univ, Dept Chem, Vaddeswaram 522502, Guntur, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 149卷

关键词：

Schizandrin; Synthesis; Cytotoxic activities; Flow cytometric analysis; Docking; NATURAL-PRODUCTS; SCHISANDRA-GRANDIFLORA; CIPADESSA-BACCIFERA; LIGNANS; WILSONIANA; LIMONOIDS; ANALOGS; CANCER;

D O I：

10.1016/j.ejmech.2018.02.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38 mu M which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：182 / 192

页数：11

共 28 条

[1]

[Anonymous], 2011, 10 IARC CANC BAS INT

[2] Synthesis and biological evaluation of new taxoids derived from 2-deacetoxytaxinine J [J].

Botta, Maurizio ;

Armaroli, Silvia ;

Castagnolo, Daniele ;

Fontana, Gabriele ;

Pera, Paula ;

Bombardelli, Ezio .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (06) :1579-1583

[3] Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration [J].

Chan, Kin Tak ;

Meng, Fan Yan ;

Li, Qian ;

Ho, Cheong Yip ;

Lam, Tsz Shan ;

To, Yu ;

Lee, Wai Him ;

Li, Miao ;

Chu, Kee Hung ;

Toh, Melvin .

CANCER LETTERS, 2010, 294 (01) :118-124

[4] Impact of Natural Products on Developing New Anti-Cancer Agents [J].

Cragg, Gordon M. ;

Grothaus, Paul G. ;

Newman, David J. .

CHEMICAL REVIEWS, 2009, 109 (07) :3012-3043

[5] Synthesis and antitumor activity of new glycosides of epipodophyllotoxin, analogues of etoposide, and NK 611 [J].

Daley, L ;

Guminski, Y ;

Demerseman, P ;

Kruczynski, A ;

Etievant, C ;

Imbert, T ;

Hill, BT ;

Monneret, C .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (23) :4475-4485

[6] Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].

Ferlay, Jacques ;

Shin, Hai-Rim ;

Bray, Freddie ;

Forman, David ;

Mathers, Colin ;

Parkin, Donald Maxwell .

INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917

[7]

Gonzales Gustavo F., 2006, Anti-Cancer Agents in Medicinal Chemistry, V6, P429, DOI 10.2174/187152006778226486

[8] Synthesis and Insecticidal Activity of Some Novel Fraxinellone-Based Esters [J].

Guo, Yong ;

Yan, Yuanyuan ;

Yu, Xiang ;

Wang, Yi ;

Zhi, Xiao-Yan ;

Hu, Ying ;

Xu, Hui .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2012, 60 (28) :7016-7021

[9] Synthesis and the hepatoprotective activity of dibenzocyclooctadiene lignan derivatives [J].

He, Tao ;

Wang, Qing-Yao ;

Shi, Jing-Zhen ;

Fan, Tian-Yun ;

Yan, Chen ;

Huang, Lie-Jun ;

Liu, Sheng ;

Hao, Xiao-Jiang ;

Mu, Shu-Zhen .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (07) :1808-1811

[10] Synthesis and Antitumor Evaluation of Nitrovinyl Biphenyls: Anticancer Agents Based on Allocolchicines [J].

Jain, Nishant ;

Yada, Divya ;

Shaik, Thokhir B. ;

Vasantha, Galanki ;

Reddy, P. Surendra ;

Kalivendi, Shasi V. ;

Sreedhar, B. .

CHEMMEDCHEM, 2011, 6 (05) :859-868

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