Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters

被引：13

作者：

Milunovic, Miljan N. M. ^{[1
]}

Palamarciuc, Oleg ^{[2
]}

Sirbu, Angela ^{[2
]}

Shova, Sergiu ^{[3
]}

Dumitrescu, Dan ^{[4
]}

Dvoranova, Dana ^{[5
]}

Rapta, Peter ^{[5
]}

Petrasheuskaya, Tatsiana V. ^{[6
,7
]}

Enyedy, Eva A. ^{[6
,7
]}

Spengler, Gabriella ^{[7
,8
]}

Ilic, Marija ^{[9
,10
,11
]}

Sitte, Harald H. ^{[10
]}

Lubec, Gert ^{[11
]}

Arion, Vladimir B. ^{[1
]}

机构：

[1] Univ Vienna, Inst Inorgan Chem, Fac Chem, Wahringer Str 42, A-1090 Vienna, Austria

[2] Moldova State Univ, Dept Chem, A Mateevici St 60, MD-2009 Kishinev, Moldova

[3] Petru Poni Inst Macromol Chem, Lab Inorgan Polymers, Aleea Grigore Ghica Voda,Nr 41A, Iasi 700487, Romania

[4] Elettra Sincrotrone Trieste SCpA, Str Statale 14-km 163,5 AREA Sci Pk, I-34149 Trieste, Italy

[5] Slovak Univ Technol Bratislava, Inst Phys Chem & Chem Phys, Fac Chem & Food Technol, Radlinskeho 9, SK-81237 Bratislava, Slovakia

[6] Univ Szeged, Dept Inorgan & Analyt Chem, Interdisciplinary Excellence Ctr, Dom Ter 7, H-6720 Szeged, Hungary

[7] Univ Szeged, MTA SZTE Lendulet Funct Met Complexes Res Grp, Dom Ter 7, H-6720 Szeged, Hungary

[8] Univ Szeged, Dept Med Microbiol & Immunobiol, Dom Ter 10, H-6720 Szeged, Hungary

[9] Univ Vienna, Dept Pharmaceut Chem, Fac Life Sci, A-1090 Vienna, Austria

[10] Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria

[11] Paracelsus Private Med Univ, Neuroprote, A-5020 Salzburg, Austria

来源：

BIOMOLECULES | 2020年 / 10卷 / 09期

基金：

奥地利科学基金会;

关键词：

thiosemicarbazones; copper(II) complexes; cytotoxicity; organic cation transporters (OCT1-3); inhibitors; SELECTIVE ANTITUMOR-ACTIVITY; IRON CHELATORS; IN-VITRO; THIOSEMICARBAZONE CHELATORS; ANTIPROLIFERATIVE ACTIVITY; CELLULAR ACCUMULATION; COMPLEXES; RESISTANCE; DRUG; DERIVATIVES;

D O I：

10.3390/biom10091213

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：

A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H2L (R)]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HL (R))Cl]Cl (1-4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1-3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order:3>2>4>cisplatin>1>> [H2L (R)]Cl. The copper(II) complexes showed marked interaction with OCT1-3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.

引用

页码：1 / 30

页数：30

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