A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer.


:Recent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the other cancer cells has been the most important topic during the last decade. In the present study, we evaluated the cytotoxic activity of trans-[PtCl2(2-hepy)2] [2-hepy=2-(2-hydroxyethyl) pyridine] complex and the mechanism of cell death in breast CSCs. Stemness markers, Oct-4 and Sox2, were determined in mammospheres by western blotting. Cytotoxicity was assessed using the ATP viability assay. Cell death was fluorescently visualized and further confirmed by flow cytometry as well as gene expression analysis. The Pt(II) complex significantly reduced the cell viability, prevented mammosphere formation and disrupted mammosphere structures in a dose-dependent manner (0-100μM). The mode of cell death was apoptosis and it was shown by the presence of caspase 3/7 activity, Annexin V-FITC positivity, decreased mitochondrial membrane potential and increased expressions of pro-apoptotic genes (TNFRSF10A and HRK). Interestingly, necroptosis was also observed by the evidence of increased MLKL expression. In conclusion, the Pt(II) complex seems to be a highly promising anticancer compound due to its promising cytotoxic activity on CSCs. Therefore, it deserves in vivo further studies for the proof-of-concept.


Bioorg Med Chem


Aztopal N,Karakas D,Cevatemre B,Ari F,Icsel C,Daidone MG,Ulukaya E




Has Abstract


2017-01-01 00:00:00














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    abstract::Dicationic 2,6-diphenylpyrazines, aza-analogues and prodrugs were synthesized; evaluated for DNA affinity, activity against Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.) in vitro, efficacy in T. b. r. STIB900 acute and T. b. brucei GVR35 CNS mouse models. Most diamidines gave poly(dA-dT)2...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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  • Synthesis and biological evaluation of novel flexible nucleoside analogues that inhibit flavivirus replication in vitro.

    abstract::Flaviviruses, such as Dengue (DENV) and Zika (ZIKV) viruses, represent a severe health burden. There are currently no FDA-approved treatments, and vaccines against most flaviviruses are still lacking. We have developed several flexible analogues ("fleximers") of the FDA-approved nucleoside Acyclovir that exhibit activ...

    journal_title:Bioorganic & medicinal chemistry

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    authors: Thames JE,Waters CD 3rd,Valle C,Bassetto M,Aouadi W,Martin B,Selisko B,Falat A,Coutard B,Brancale A,Canard B,Decroly E,Seley-Radtke KL

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  • Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation.

    abstract::Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity a...

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    authors: Dreyton CJ,Anderson ED,Subramanian V,Boger DL,Thompson PR

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    abstract::The combretastatins have received significant attention because of their simple chemical structures, excellent antitumor efficacy and novel antivascular mechanisms of action. Herein, we report the synthesis of 20 novel acetyl analogs of CA-4 (1), synthesized from 3,4,5-trimethoxyphenylacetone that comprises the A ring...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Babu B,Lee M,Lee L,Strobel R,Brockway O,Nickols A,Sjoholm R,Tzou S,Chavda S,Desta D,Fraley G,Siegfried A,Pennington W,Hartley RM,Westbrook C,Mooberry SL,Kiakos K,Hartley JA,Lee M

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  • A quantitative structure-activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gayathri P,Pande V,Sivakumar R,Gupta SP

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  • Irreversibly inhibitory kinetics of 3,5-dihydroxyphenyl decanoate on mushroom (Agaricus bisporus) tyrosinase.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Qiu L,Chen QX,Wang Q,Huang H,Song KK

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  • Bis-pyrene-labeled molecular beacon: a monomer-excimer switching probe for the detection of DNA base alteration.

    abstract::A new bis-pyrene-labeled oligonucleotide probe (BP-probe) has been designed for the detection of a single base mismatch in single strand (ss) DNA as a target. The sequence of BP-probe was chosen to form stem-loop structure similar to a molecular beacon (MB-probe), yielding bis-pyrene-labeled molecular beacon (BP-MB-pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yamana K,Ohshita Y,Fukunaga Y,Nakamura M,Maruyama A

    更新日期:2008-01-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fukushima H,Hiratate A,Takahashi M,Mikami A,Saito-Hori M,Munetomo E,Kitano K,Chonan S,Saito H,Suzuki A,Takaoka Y,Yamamoto K

    更新日期:2008-04-01 00:00:00

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    pub_type: 杂志文章


    authors: Wang Y,Yuan H,Wright SC,Wang H,Larrick JW

    更新日期:2003-04-03 00:00:00

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    abstract::A series of novel benzofuran-dihydropyridine hybrids were designed by molecular hybridization approach and evaluated for bone anabolic activities. Among the screened library, ethyl 4-(7-(sec-butyl)-2-(4-methylbenzoyl)benzofuran-5-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (compound 21) significant...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Modukuri RK,Choudhary D,Gupta S,Rao KB,Adhikary S,Sharma T,Siddiqi MI,Trivedi R,Sashidhara KV

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ozensoy O,Nishimori I,Vullo D,Puccetti L,Scozzafava A,Supuran CT

    更新日期:2005-11-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wu H,Micca PL,Makar MS,Miura M

    更新日期:2006-08-01 00:00:00

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    pub_type: 杂志文章


    authors: Luo Y,Qiu KM,Lu X,Liu K,Fu J,Zhu HL

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    abstract::γ-Amino butyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). A malfunction of the GABAergic neurotransmission is connected to several neuronal disorders like epilepsy, Alzheimer's disease, neuropathic pain, and depression. One possibility to enhance GABA levels in...

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    authors: Quandt G,Höfner G,Wanner KT

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    abstract::Aminoglycoside antibiotics have recently emerged as an intriguing family of RNA binding molecules and they became leading structures for the design of novel RNA ligands. The demystification of the aminoglycoside-RNA recognition phenomenon is required for the development of superior binders. To explore the existence of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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  • Synthesis and insecticidal activity of chromanone and chromone analogues of diacylhydrazines.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2007-03-01 00:00:00

  • Triterpene sapogenin-polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains.

    abstract::Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charge...

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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Vogel KW,Stark LM,Mishra PK,Yang W,Drueckhammer DG

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Méndez-Lucio O,Pérez-Villanueva J,Castillo R,Medina-Franco JL

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tunçbilek M,Ateş-Alagöz Z,Altanlar N,Karayel A,Ozbey S

    更新日期:2009-02-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ari F,Aztopal N,Icsel C,Yilmaz VT,Guney E,Buyukgungor O,Ulukaya E

    更新日期:2013-11-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang JQ,Kreklau EL,Bailey BJ,Erickson LC,Zheng QH

    更新日期:2005-10-15 00:00:00

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    abstract::1,11-Didechloro-6-methyl-4'-O-demethyl rebeccamycin (JDC-108), a rebeccamycin analog possessing potent anti-tumor activities, was prepared via a concise one-pot strategy in good yield. The interaction between JDC-108 and human serum albumin (HSA) was studied by spectroscopic methods including fluorescence spectroscopy...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cui F,Qin L,Zhang G,Liu X,Yao X,Lei B

    更新日期:2008-08-15 00:00:00

  • Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3.

    abstract::The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived fro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ikeda M,Takahashi K,Dan A,Koyama K,Kubota K,Tanaka T,Hayashi M

    更新日期:2000-08-01 00:00:00

  • Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta H

    更新日期:2019-07-15 00:00:00

  • 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis.

    abstract::A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cesarini S,Spallarossa A,Ranise A,Bruno O,Arduino N,Bertolotto M,Dallegri F,Tognolini M,Gobbetti T,Barocelli E

    更新日期:2009-05-15 00:00:00

  • Inhibition of monoamine oxidase B by selected benzimidazole and caffeine analogues.

    abstract::We have recently reported that a series of (E)-8-styrylcaffeines and (E)-2-styrylbenzimidazoles are moderate to very potent competitive inhibitors of monoamine oxidase B (MAO-B). The most potent member of the series was found to be (E)-8-(3-chlorostyryl)caffeine (CSC) with an enzyme-inhibitor dissociation constant (K(...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: van den Berg D,Zoellner KR,Ogunrombi MO,Malan SF,Terre'Blanche G,Castagnoli N Jr,Bergh JJ,Petzer JP

    更新日期:2007-06-01 00:00:00

  • Tessaric acid derivatives induce G2/M cell cycle arrest in human solid tumor cell lines.

    abstract::A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably g...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: León LG,Donadel OJ,Tonn CE,Padrón JM

    更新日期:2009-09-01 00:00:00