Tuning the Activity of Platinum(IV) Anticancer Complexes through Asymmetric Acylation

Chin, Chee Fei; Tian, Quan; Setyawati, Magdiel Inggrid; Fang, Wanru; Tan, Emelyn S. Q.; Leong, David Tai; Ang, Wee Han

doi:10.1021/jm300580y

Cited by 96 publications

(80 citation statements)

References 50 publications

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“…35,36 Inert Pt(IV) prodrugs and the combination between Pt(II) drugs and drug carriers have been widely studied. [37][38][39][40] Pt(IV)-conjugated CNTs were constructed to effectively deliver cisplatin (cis-dichlorodiammineplatinum, CDDP). [41][42][43][44][45][46][47][48] Dhar et al 41 developed amine-functionalized SWCNTs (SWCNTs-phospholipid-PEG-NH 2 ) as a "longboat delivery system" for Pt-based CDDP.…”

Section: Cnts As Pt-based Drug Carriersmentioning

confidence: 99%

Carbon nanotubes as cancer therapeutic carriers and mediators

Son¹,

Hong²,

Lee³

2016

IJN

206

106

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Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug–CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy.

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Section: Cnts As Pt-based Drug Carriersmentioning

confidence: 99%

Carbon nanotubes as cancer therapeutic carriers and mediators

Son¹,

Hong²,

Lee³

2016

IJN

206

106

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“…As Pt IV complexes are octahedrally configured, and therefore have six binding sites for ligands, there are numerous possibilities for controlling the reduction parameters. Recently, an increasing number of Pt IV compounds were synthesised with mixed axial ligands, [13][14][15] opening up new, mostly unexplored ligand spheres. Compared with the well-known symmetrically dicarboxylated complexes (especially satraplatin), these unsymmetrically substituted complexes offer, apart from a different solubility and lipophilicity, a distinctly diverging rate of reduction.…”

Section: Introductionmentioning

confidence: 99%

Influence of reducing agents on the cytotoxic activity of platinum(iv) complexes: induction of G2/M arrest, apoptosis and oxidative stress in A2780 and cisplatin resistant A2780cis cell lines

et al. 2015

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The concept of Pt(IV) prodrug design is one advanced strategy to increase the selectivity for cancer cells and to reduce systemic toxicity in comparison to established platinum-based chemotherapy. Pt(IV) complexes are thought to be activated by reduction via physiological reductants, such as ascorbic acid or glutathione. Nevertheless, only few investigations on the link between the reduction rate, which is influenced by the reductant, and the ligand sphere of the Pt(IV) metal centre have been performed so far. Herein, we investigated a set of Pt(IV) compounds with varying rates of reduction with respect to their cytotoxicity and drug accumulation in A2780 and A2780cis ovarian cancer cell lines, their influence on the cell cycle, efficiency of triggering apoptosis, and ability to interfere with plasmid DNA (pUC19). The effects caused by Pt(IV) compounds were compared without or with extracellularly added ascorbic acid and glutathione (or its precursor N-acetylcysteine) to gain understanding of the impact of increased levels of the reductant on the activity of such complexes. Our results demonstrate that reduction is required prior to plasmid interaction. Furthermore, the rate of reduction is crucial for the efficiency of this set of Pt(IV) compounds. The substances that are reduced least likely showed similar performances, whereas the fastest reducing substance was negatively affected by an increased extracellular level of reducing agents, with reduced cytotoxicity and lower efficiency in inducing apoptosis and G2/M arrest. These results confirm the connection between reduction and activity, and prove the strong impact of the reduction site on the activity of Pt(IV) complexes.

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“…顺铂与癌细胞 DNA 分子中的嘌呤 N7 原子络合, 可阻止癌细胞 DNA 的复制, 导致细胞死亡. 但是许多铂类抗癌药物发挥抗癌活性对正常细胞同样具有细胞毒性, 唑类化合物不仅具有广泛的生物活性, 而且细胞毒副作用小, 在药物化学中应用宽广, 因此尝试用不同的唑类配体来合成顺铂类似物从而降低细胞毒性具有重要意义 [54,55] . 一分子噻唑类化合物 1a 或异噁唑类化合物 1b 分别与一分子 PtCl 2 形成的金属络合物超分子对正常细胞的毒性比顺铂大大降低, 并且 1b 的铂(II)络合物超分子对卵巢癌(Ovarian carcinoma) CH1 细胞抑制能力很强, 半数抑制浓度 IC 50 值为 0.37 μmol/L, 抗癌活性是 1a 的铂(II)超分子的两倍 [56] .…”

Section: 唑类超分子作为抗癌药物unclassified

Current Researches and Applications of Azole-BasedSupermolecules as Medicinal Agents

Cheng¹,

Wang²,

Addla³

et al. 2016

Chin. J. Org. Chem.

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Noncovalent bond forces-based supramolecular chemistry grows quite rapidly and has been revealed to have extensively potential applications and huge development values in chemistry, physics, materials and information science, medicine and so on. Azole compounds such as imidazoles, thiazoles, oxazoles, pyrazoles, triazoles, tetrazoles and carbazoles containing special nitrogen aromatic heterocyclic structure, can exert non-covalent forces to form supramolecular complexes with inorganic and/or organic compounds and exhibit broad biological activity. In recent years, heterocyclic azole-based supramolecular complexes have been expeditiously expanding in the field of medicine, and have become a quite hot topic. Combined with our work and referring to other literature in recent 5 years, this paper systematically reviews the researches and applications of azole-based supermolecules as medicinal agents including anticancer, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, anti-inflammatory drugs and other ones. Finally, the perspectives of the future development of azole-based supermolecules as medicinal agents are also presented.

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Tuning the Activity of Platinum(IV) Anticancer Complexes through Asymmetric Acylation

Cited by 96 publications

References 50 publications

Carbon nanotubes as cancer therapeutic carriers and mediators

Carbon nanotubes as cancer therapeutic carriers and mediators

Influence of reducing agents on the cytotoxic activity of platinum(iv) complexes: induction of G2/M arrest, apoptosis and oxidative stress in A2780 and cisplatin resistant A2780cis cell lines

Current Researches and Applications of Azole-BasedSupermolecules as Medicinal Agents

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