2, 4, 5-Trideoxyhexopyranosides derivatives of diphyllin: Synthesis and anticancer activity

被引：5

作者：

Cai, Rui ^{[1
]}

Li, Yu ^{[2
]}

Zhu, Li ^{[2
]}

Wei, Caiyan ^{[2
]}

Bao, Xiaofeng ^{[2
]}

Zhao, Yu ^{[2
]}

机构：

[1] Nanjing Med Univ, Changzhou Maternal & Child Hlth Care Hosp, Dept Pharm, Changzhou Med Ctr, Changzhou, Jiangsu, Peoples R China

[2] Nantong Univ, Sch Pharm, Nantong 226001, Peoples R China

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2022年 / 100卷 / 02期

关键词：

2; 4; 5-trideoxyhexopyranosides; diphyllin; molecular docking; synthesis; V-ATPase inhibitor; DE-NOVO SYNTHESIS; INHIBITORS; ATPASES;

D O I：

10.1111/cbdd.14095

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Diphyllin and its natural derivatives were identified as potent vacuolar H+-ATPase (V-ATPase) inhibitors. In this study, twelve 2, 4, 5-trideoxyhexopyranosides derivatives of diphyllin were synthesized. Most of these compounds showed potent abilities to inhibit the growth of HT-29, MCF-7, HepG2 cancer cells with IC50 values at submicromolar concentration. The compounds 5c3 and 5c4 showed the best inhibitory activity on breast cancer cell lines MCF-7 with IC50 values of 0.09 and 0.10 mu M. Compounds 5c3 and 5c4 showed similar V-ATPase inhibitory potency to diphyllin. Molecular docking showed that a hydrogen bond was found between the hydroxyl of 5c3 and SerA534 in the pocket of the V-ATPase receptor.

引用

页码：256 / 266

页数：11

共 23 条

[1] Synthesis of photoactivable inhibitors of osteoclast vacuolar ATPase [J].

Biasotti, B ;

Dallavalle, S ;

Merlini, L ;

Farina, C ;

Gagliardi, S ;

Parini, C ;

Belfiore, P .

BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (10) :2247-2254

[2] BAFILOMYCINS - A CLASS OF INHIBITORS OF MEMBRANE ATPASES FROM MICROORGANISMS, ANIMAL-CELLS, AND PLANT-CELLS [J].

BOWMAN, EJ ;

SIEBERS, A ;

ALTENDORF, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (21) :7972-7976

[3] Recent Insights into the Structure, Regulation, and Function of the V-ATPases [J].

Cotter, Kristina ;

Stransky, Laura ;

McGuire, Christina ;

Forgac, Michael .

TRENDS IN BIOCHEMICAL SCIENCES, 2015, 40 (10) :611-622

[4] Atp6v1c1 May Regulate Filament Actin Arrangement in Breast Cancer Cells [J].

Feng, Shengmei ;

Cai, Ming ;

Liu, Pengcheng ;

Wei, Li ;

Wang, Jinshen ;

Qi, Jin ;

Deng, Lianfu .

PLOS ONE, 2014, 9 (01)

[5] The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila [J].

Hiesinger, PR ;

Fayyazuddin, A ;

Mehta, SQ ;

Rosenmund, T ;

Schulze, KL ;

Zhai, RG ;

Verstreken, P ;

Cao, Y ;

Zhou, Y ;

Kunz, J ;

Bellen, HJ .

CELL, 2005, 121 (04) :607-620

[6] Inhibitors of V-ATPases: old and new players [J].

Huss, Markus ;

Wieczorek, Helmut .

JOURNAL OF EXPERIMENTAL BIOLOGY, 2009, 212 (03) :341-346

[7] Synthesis and Structure-Activity Relationship Study of 5a-Carbasugar Analogues of SL0101 [J].

Li, Mingzong ;

Li, Yu ;

Mrozowski, Roman M. ;

Sandusky, Zachary M. ;

Shan, Mingde ;

Song, Xiwen ;

Wu, Bulan ;

Zhang, Qi ;

Lannigan, Deborah A. ;

O'Doherty, George A. .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (01) :95-99

[8] 2, 4, 5-Trideoxyhexopyranosides Derivatives of 4′-Demethylepipodophyllotoxin: De novo Synthesis and Anticancer Activity [J].

Lu, Yapeng ;

Zhu, Li ;

Cai, Rui ;

Li, Yu ;

Zhao, Yu .

MEDICINAL CHEMISTRY, 2022, 18 (01) :130-139

[9] Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents [J].

Lu, Yapeng ;

Wang, Lu ;

Wang, Xinyang ;

Yuan, Haoliang ;

Zhao, Yu .

FUTURE MEDICINAL CHEMISTRY, 2019, 11 (23) :3015-3027

[10] The vacuolar (H+)-atpases -: Nature's most versatile proton pumps [J].

Nishi, T ;

Forgac, M .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (02) :94-103

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