103-40-2Relevant articles and documents
Self-assembly of a 5-fluorouracil-dipeptide hydrogel
Sun, Yuan,Kaplan, Jonah A.,Shieh, Aileen,Sun, Hui-Lung,Croce, Carlo M.,Grinstaff, Mark W.,Parquette, Jon R.
, p. 5254 - 5257 (2016)
The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23.
Preferential binding of E. coli with type 1 fimbria to D-mannobiose with the Manα1→2Man structure
Ajisaka, Katsumi,Yuki, Kaoru,Sato, Kaori,Ishii, Nozomi,Matsuo, Ichiro,Kuji, Ryo,Miyazaki, Tatsuo,Furukawa, Kiyoshi
, p. 128 - 134 (2016)
Manα1→2Man, Manα1→3Man, Manα1→4Man, and Manα1→6Man were converted to the glycosylamine derivatives. Then, they were mixed with monobenzyl succinic acid to obtain their amide derivatives. After removing the benzyl group by hydrogenation, the succinylamide derivatives were coupled with the hydrazino groups on BlotGlyco beads in the presence of water-soluble carbodiimide. D-Mannobiose-linked beads were incubated with fluorescence-labeled Escherichia coli with type 1 fimbria, and the number of the fluorescent dots associated with the beads was counted in order to determine the binding preference among D-mannobiose isomers. The results showed that the bacteria bind strongly to Manα1→2Man1→beads, Man- α1→3Man1→beads, Manα1→4Man1→beads, and Manα1→6Man1→beads, in order. In the presence of 0.1 M methyl α-D-mannopyranoside, most of the bacteria failed to bind to these beads. These results indicate that E. coli with type 1 fimbria binds to all types of D-mannobiose isomers but preferentially to Manα1→2Man disaccharide.
A General Strategy for the Preparation of Thalidomide-Conjugate Linkers
Papatzimas, James W.,Gorobets, Evgueni,Brownsey, Duncan K.,Maity, Ranjan,Bahlis, Nizar J.,Derksen, Darren J.
, p. 2881 - 2885 (2017)
The synthesis of small-molecule linkers for installation of thalidomide-based conjugates is described. Linker properties have been recognized as vital to conjugate success in drug discovery and delivery systems. These small-molecule tethers act as linkages between molecules, can also aid in cell permeability, and act as solubilizing agents. This work shows our progress in synthesizing conjugates with a variety of linker characteristics. The adaptability and manipulation of these and other linkers holds potential in improving synthetic control of chemical connectivities toward therapeutic development.
From Inhibition to Degradation: Targeting the Antiapoptotic Protein Myeloid Cell Leukemia 1 (MCL1)
Papatzimas, James W.,Gorobets, Evgueni,Maity, Ranjan,Muniyat, Mir Ishruna,Maccallum, Justin L.,Neri, Paola,Bahlis, Nizar J.,Derksen, Darren J.
, p. 5522 - 5540 (2019)
Protein-protein interactions (PPIs) have emerged as significant targets for therapeutic development, owing to their critical nature in diverse biological processes. An ideal PPI-based target is the protein myeloid cell leukemia 1 (MCL1), a critical prosurvival factor in cancers such as multiple myeloma where MCL1 levels directly correlate to disease progression. Current strategies for halting the antiapoptotic properties of MCL1 revolve around inhibiting its sequestration of proapoptotic factors. Existing inhibitors disrupt endogenous regulatory proteins; however, this strategy actually leads to an increase of MCL1 protein levels. Here, we show the development of hetero-bifunctional small molecules capable of selectively targeting MCL1 using a proteolysis targeting chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon ubiquitination pathway, making these PROTACs a first step toward a new class of antiapoptotic B-cell lymphoma 2 family protein degraders.
Esterification of dicarboxylic acids with benzyl alcohol under the action of the microwave radiation
Aver'yanov,Batrakova,Samuilov,Spiridonova,Kochnev,Galibeev,Gnezdilov
, p. 1920 - 1923 (2008)
Reaction of dicarboxylic acid with benzyl alcohol under the microwave irradiation proceeds faster as compared to the thermal conditions. The main reaction products are alkyl dicarboxylates, and the monoester and dibenzyl ether are formed as the side products. A proposal about the nature of the nonthermal effect in the reactions stimulated by the microwave irradiation is considered.
Biotin and glucose dual-targeting, ligand-modified liposomes promote breast tumor-specific drug delivery
Fu, Qiuyi,Guo, Li,Huang, Mengyi,Peng, Yao,Pu, Yanchi,Wu, Yong,Zheng, Yongxiang
, (2020)
Breast cancer is the second leading cause of cancer-related deaths in women. Ligand-modified liposomes are used for breast tumor-specific drug delivery to improve the efficacy and reduce the side effects of chemotherapy; however, only a few liposomes with high targeting efficiency have been developed because the mono-targeting, ligand-modified liposomes are generally unable to deliver an adequate therapeutic dose. In this study, we designed biotin-glucose branched ligand-modified, dual-targeting liposomes (Bio-Glu-Lip) and evaluated their potential as a targeted chemotherapy delivery system in vitro and in vivo. When compared with the non-targeting liposome (Lip), Bio-Lip, and Glu-Lip, Bio-Glu-Lip had the highest cell uptake in 4T1 cells (3.00-fold, 1.60-fold, and 1.95-fold higher, respectively) and in MCF-7 cells (2.63-fold, 1.63-fold, and 1.85-fold higher, respectively). The subsequent cytotoxicity and in vivo assays further supported the dual-targeting liposome is a promising drug delivery carrier for the treatment of breast cancer.
Synthesis of novel γ-ketoesters from succinic anhydride
Iqbal, Muhammad,Baloch, Imam Bakhsh,Baloch, Musa Kaleem
, p. 9701 - 9703 (2013)
Four alkyl g-ketohexanoates (3a-3d) have been prepared from succinic anhydride employing a three step reaction strategy. In the first step using p-toluene sulfonic acid as catalyst, the ring of succinic anhydride was opened with isopropyl, isobutyl, isopentyl and benzyl alcohols, respectively to form alkyl hydrogen succinates (1a-1d). In the 2nd step these alkyl hydrogen succinates on treatment with SOCl2 yielded 4-alkoxy-4-ketobutanoyl chlorides (2a-2d). The acid halides thus obtained, on reaction with diethyl cadmium led to require g-ketoesters. All the synthesised compounds were characterized by recording and analyzing 1H, 13C NMR, IR spectra and mass measurements.
Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs
Liu, Liang-Quan,Hong, Pei-Xi,Song, Xing-Hai,Zhou, Chang-Cui,Ling, Rui,Kang, Yi,Qi, Qing-Rong,Yang, Jun
supporting information, p. 7857 - 7866 (2020/08/21)
In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (3e, 3g, and 3j) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia. Their molar dose, onset time, and anesthesia duration time were comparable to those of propofol, helping to maintain the clinical benefits of propofol. The experimental results showed the potential of such compounds as water-soluble prodrugs of propofol.
