- Synthesis of aspirin-ligated cisplatin derivatives and its slow release study over MIL-101(Fe)
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An aspirin-ligated cisplatin derivative, biasplatin, was prepared from acetylsalicylic anhydride and oxoplatin in DMF. Biasplatin was synthesized from oxoplatin and aspirin anhydride as starting materials by a substitution reaction of hydroxo leaving groups in its axial position. The obtained biasplatin was fully characterized by FTIR, 1HNMR, 13CNMR, and ESI mass spectroscopy. Biasplatin entrapped into MIL-101(Fe) by suspended in DMF and stirring for 72?h at ambient temperature, known as biasplatin@MIL-101(Fe). The slow release of biasplatin and biasplatin@MIL-101(Fe) was conducted in PBS solution pH 7.20, 37?°C as media and measured by UV–Vis spectrophotometer. The release of biasplatin without loaded into MIL-101(Fe) is persistent for 3%, and biasplatin@MIL-101(Fe) is 0.05% over 72?h. A significant slow release of biasplatin@MIL-101(Fe) only 1% compared with time release of biasplatin without loaded into MIL-101(Fe).
- Rosari, Venansia Avelia,Lestari, Witri Wahyu,Firdaus, Maulidan
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- Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin
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Para-sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin. Furthermore, it has been characterized using1 H NMR, mass spectrometry, elemental analysis, and UHPLC. A host-guest complex of asplatin and p-sulfocalix[4]arene (PSC4) has been developed and characterized using UV, Job’s plot analysis, HPLC, and density functional theory (DFT) calculations. The experimental and computational investigations propose that a 1:1 complex between asplatin and PSC4 is formed. The stability constant of the designed complex has been determined using Job’s plot and UHPLC and computed to be 9.1 × 104 M–1 and 8.7 × 104 M?1, which corresponds to a free energy of complexation of ?6.8 kcal mol–1, while the calculated value for the inclusion free energy is ?13.2 kcal mol?1. Both experimentally and theoretically estimated complexation free energy show that a stable host-guest complex can be formed in solution. The in vitro drug release study displayed the ability of the complex to release its cargo at a cancerous pH (pH of 5.5). Additionally, the asplatin/PSC4 complex is shown to be biocompatible when tested on human skin fibroblast noncancerous cells, demonstrating the highest in vitro cytotoxic activity against (MCF-7), cervical (HeLa), and lung cancer cells (A-549), with IC50 values of 0.75, 2.15, and 3.60 μg/mL, respectively. This is as compared to either cisplatin (IC50 of 5.47, 5.94 and 9.61 μg/mL, respectively) or asplatin (IC50 of 1.54, 5.05 and 3.91 μg/mL, respectively). On the other hand, the free asplatin exhibited higher cytotoxicity on cancerous cells and lower toxicity on noncancerous cells. The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent.
- Azzazy, Hassan Mohamed El-Said,Fahmy, Sherif Ashraf,Fawzy, Iten M.,Grande, Giulia,Mandour, Asmaa A.,Ponte, Fortuna,Sicilia, Emilia
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- Ctc-[Pt(NH3)2(cinnamate)(valproate)Cl2] is a highly potent and low-toxic triple action anticancer prodrug
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Pt(iv) prodrugs have gained tremendous attention due to their indisputable advantages compared to cisplatin. Herein, new Pt(iv) derivatives with cinnamic acid at the first axial position, and inhibitor of matrix metalloproteinases-2 and-9, histone deacetylase, cyclooxygenase or pyruvate dehydrogenase at the second axial position are constructed to develop multi-action prodrugs. We demonstrate that Pt(iv) prodrugs are reducible and have superior antiproliferative activity with IC50 values at submicromolar concentrations. Notably, Pt(iv) prodrugs exhibit highly potent anti-tumour activity in an in vivo breast cancer model. Our results support the view that a triple-action Pt(iv) prodrug acts via a synergistic mechanism, which involves the effects of CDDP and the effects of axial moieties, thus jointly leading to the death of tumour cells. These findings provide a practical strategy for the rational design of more effective Pt(iv) prodrugs to efficiently kill tumour cells by enhancing their cellular accumulation and tuning their canonical mechanism.
- Li, Yang,Shi, Shan,Zhang, Shurong,Gan, Zongjie,Wang, Xin,Zhao, Xudong,Zhu, Yijian,Cao, Meiting,Wang, Xiaoyue,Li, Wei
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supporting information
p. 11180 - 11188
(2021/08/25)
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- Acid anhydrides and the unexpected N,N-diethylamides derived from the reaction of carboxylic acids with Ph3P/I2/Et3N
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The formation of acid anhydrides from the phosphorous-mediated activation of carboxylic acids was investigated. Under various systems, activation of benzoic acid in the presence of base led to the formation of benzoic anhydride at different rates depending on the reactivity of the reagents. Using the Ph3P-I2/Et3N combination, most aryl acids were converted into the corresponding anhydrides in high yields within 5-10 min. However, for nitro-substituted derivatives, unexpectedly, N,N-diethylamides were isolated without anhydride formation. These results indicated the pronounced effect of substituents in governing these potential side reactions which can significantly affect the yields of acylation reactions promoted by phosphonium species.
- Phakhodee, Wong,Duangkamol, Chuthamat,Wangngae, Sirilak,Pattarawarapan, Mookda
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supporting information
p. 325 - 328
(2016/01/12)
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- PRODRUG FOR RELEASE OF CISPLATIN AND CYCLOOXYGENASE INHIBITOR
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Pt(IV) prodrugs include one or more conjugated cyclooxygenase inhibitor. Reduction of Pt(IV) to Pt(II) can result cisplatin and a cyclooxygenase inhibitor. For proof of concept, a Pt(IV) prodrug that can produce cisplatin and aspirin, Platin-A, was synthesized. Platin-A exhibited excellent anticancer and anti-inflammatory properties, which were better than the combination of free formulation of cisplatin and aspirin.
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Paragraph 0098
(2015/06/25)
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- A convenient method for synthesis of symmetrical acid anhydrides from carboxylic acids with trichloroacetonitrile and triphenylphosphine
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Various carboxylic acids are converted into the corresponding carboxylic acid anhydrides treated with trichloroacetonitrile and triphenylphosphine in the presence of triethylamine at room temperature.
- Kim,Jang
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p. 395 - 399
(2007/10/03)
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- Synthesis and Hydrolysis of New Aspirin- and Triflusal-Derived Ortho Esters and Anhydrides
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Ten new 2-substituted 2-methyl-2-oxy-4H-1,3-benzodioxin-4-ones, 4a-i and 6, have been synthesized and their rate constants of pseudo-first-order non enzymatic hydrolysis determined.One of the compounds, 2-(2-acetoxybenzoyloxy)-2-methyl-4H-1,3-benzodioxin-4-one, 6, is a new anhydride of aspirin.The analogous triflusal derivative, 10, has also been synthesized.
- Fallborg, Lise,Senning, Alexander
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p. 514 - 520
(2007/10/02)
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