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New Biological Targets for the Treatment of Leishmaniasis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Fabrizio Carta, Andrea Angeli, Christian D.-T. Nielsen, Claudiu T. Supuran, Agostino Cilibrizzi
Both methodologies rely upon the activation of the carboxylic acid moiety to a redox active ester which could be isolated or reacted in situ. Even though the mechanism proceeds via a radical pathway (confirmed by Aggarwal’s studies employing radical clock experiments), the methodology could functionalize a variety of complex natural products, demonstrating exquisite control not often associated with traditional radical chemistry (Figures 18A and B). Of note, a borono-vancomycin analogue was obtained as a single diastereomer from vancomycin (Li et al. 2017). Aggarwal (A) and Baran’s (B) decarboxylative borylations. THF = tetrahydrofuran; DMF = dimethylformamide; B2Pin2 = bis(pinacolato)diboron; DMAc = N,N-dimethylacetamide.
Hydrotropic Polymer Micelles for Cancer Therapeutics
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Sang Cheon Lee, Kang Moo Huh, Tooru Ooya, Kinam Park
Each hydrotropic agent is effective in increasing the water solubility of selected hydrophobic drugs, and no hydrotropic agents were found that are universally effective. Therefore, the structure–activity relationship between selected pairs of the hydrotropic agent and the drug is another important concern to discuss. Park et al. reported on the intensive studies of the elucidation of structure–activity relationship for the hydrotropic solubilization of paclitaxel using not only nicotinamide and its analogues as aromatic amides, but also various ureas as aliphatic amides.25 They showed that nicotinamide enhanced the aqueous solubility of paclitaxel to a greater extent than the aliphatic analogues of nicotinamide such as nipecotamide and N,N-dimethylacetamide. In addition, the aqueous solubility of paclitaxel was found to be strongly dependent on the alkyl substituent on the amide nitrogen of nicotinamide. DENA of 3.5 M enhanced the aqueous solubility of paclitaxel up to 39.07 mg/mL, whereas N,N-dimethylnicotinamide showed paclitaxel solubility of 1.77 mg/mL at the same concentration. They synthesized new hydrotropic agents based on the structure of nicotinamide by varying the substituent to the amide nitrogen with a pyridine ring or an ally group. The aqueous solution of N-picolylnicotinamide (PNA) (3.5 M), having another pyridine ring as a substituent on the amide nitrogen, was highly effective in the enhancement of paclitaxel solubility (29.44 mg/mL), compared with the hydrotropic effect of nicotinamide on the paclitaxel (0.69 mg/mL). Besides, N-allylnicotinamide highly contributed to the enhancement of paclitaxel solubility (14.18 mg/mL) compared to that of N, N-dimethylnicotianmide (1.77 mg/mL). The most interesting find is that the threshold concentration where the association occurred is consistent with the threshold concentration where paclitaxel solubility began to increase.
Experimental measurement – correlation of solubility and dissolution thermodynamics study of itraconazole in pure monosolvents at various temperatures
Published in Drug Development and Industrial Pharmacy, 2021
Sachin K. Jagdale, Rajesh B. Nawale
Glycerin, propylene glycol, polyethylene glycol-200, polyethylene glycol-400, and polyethylene glycol-600 are the polymerized derivatives of ethylene glycols and are physiologically acceptable. They have the adequate pharmaceutical properties like lower toxicity, low volatility, high stability, and complete miscibility with water almost at all the proportions. They are also preferred in the design and development of various pharmaceutical oral and parenteral formulations as well as used for the preclinical and clinical studies [21,22]. 1-Methyl-2-pyrrolidone (NMP) is biodegradable solvent with high solubilizing power and used in different fields of industrial applications including pharmaceutical, synthetic, and analytical industries [23]. N, N-dimethylacetamide (DMA) is an FDA approved solvent widely used in pharmaceutical industry to improve the solubility of lipophilic, high molecular weight drugs with poor water solubility [24]. Dimethyl formamide (DMF) is an extraordinary organic compound favored as solvent in pharmaceutical industry due to its favored dissolution provided by interactions with a substrate [25]. Triacetin is reported to be used as solvent in topical and cosmetic formulations and as a carrier for fragrances and flavors [26]. Diethylene glycol is used as strong solubilizer in many products including pharmaceutical, topical, transdermal, cosmetics, nutraceuticals, and is employed for various routes of administration [27]. Carbon tetrachloride, cyclohexane, and n-hexane are used in pharmaceutical industry as reaction media, in separation and purification of synthesis products [28].
Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal liver function: a case-control study of Chinese population
Published in Biomarkers, 2018
Xianping Song, Wei Gong, Huanxi Shen, Xiuting Li, Lu Ding, Lei Han, Hengdong Zhang, Baoli Zhu, Xin Liu
N,N-dimethylacetamide (DMAc, CAS No: 127-19-5) is a powerful organic solvents widely used in polyurethane and acrylic resin industries due to its excellent dipolar solvent properties. In China, the production and application of DMAc have been showing an increasing tendency during these years. Inevitable, a growing number of workers are exposed to DMAc (Liu et al.2016). Reportedly, acute or long-term exposure to DMAc mainly causes liver injury (morphological and functional alterations) (Lee et al.2006, Jung et al.2007, Liu et al.2016). DMAc is absorbed by inhalation or through the skin and could be metabolized in the liver through a stepwise demethylation into N-methylacetamide (Perbellini et al.2003). It appears that the metabolism of DMAc is mediated via cytochrome P450 2E1 (CYP2E1) and accompanied by the production of reactive oxygen species (ROS) (Tolando et al.2001, Hempel et al.2007). ROS has been demonstrated as an inducer for the DMAc-triggered liver cells apoptosis because they could do harm to cellular DNA, proteins, and lipids (Amato et al.2001, Liu et al.2016).
Prediction of human pharmacokinetics of long half-life compounds using chimeric mice with humanised liver
Published in Xenobiotica, 2019
Maki Miyamoto, Shinji Iwasaki, Ikumi Chisaki, Sayaka Nakagawa, Nobuyuki Amano, Yohei Kosugi, Hideki Hirabayashi
Fourteen compounds were used for the PK studies. A group of compounds (up to ten compounds in one group for cassette dosing) were dissolved in N, N-dimethylacetamide (DMA) or saline and diluted with DMA/saline (1/1, v/v). A drug solution (1 mL/kg) was administered intravenously to PXB (n = 3 for UCN-01 and n = 4 for others) and SCID mice (n = 3 for UCN-01 and n = 4 for others) at 0.1 mg/kg for each compound. Blood samples were collected from the tail vein at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, and 96 h (less than 20 µL of blood volume). The plasma samples were separated by centrifugation at 1000 × g and 4 °C for 10 min. The supernatants were analysed by liquid chromatography/tandem mass spectrometry (LC-MS/MS).