4877-14-9Relevant articles and documents
Synthesis and evaluation of mono- and multi-hydroxyl low toxicity pH-sensitive cationic lipids for drug delivery
Zhao, Zheng,Yao, Weihe,Wang, Ning,Liu, Chenyu,Zhou, Hengjun,Chen, Hailiang,Qiao, Weihong
, p. 69 - 78 (2019)
Cationic lipids can easily assemble into spherical liposomes in aqueous phase which showed unique superiority in drug and gene delivery. However, the toxicity of cationic lipids is still an obstacle to application. To develop low toxicity cationic lipids, we designed two cationic lipids contained different number of hydroxyl groups. Biocompatible mono-hydroxyl and multi-hydroxyl galactose head group was respectively modified to a biodegradable quaternary amine lipid, and two novel hydroxyl cationic lipids were synthesized and characterized by MS, 1H NMR and 13C NMR. Two lipids showed good surface activity and both of them can assemble to about 80 nm stable small unilamellar vesicles (SUVs) with cholesterol in aqueous phase. Both of lipids showed relatively lower toxicity than the well-known cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). In vitro 24 h IC50 of two assemblies were more than 50 μg/mL, which were about 10 μg/mL higher than the IC50 of DOTAP. Multi-hydroxyl galactose lipids group showed much lower toxicity than mono-hydroxyl lipids group. Moreover, Both of the assemblies with lower hemolysis were nearly non-hemolytic risk under the concentration of 30 μg/mL. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that the average sizes of both doxorubicin (DOX) loaded liposomes were about 110 nm. The DOX entrapment efficiencies of galactose liposome and mono-hydroxyl liposome were 58% and 91%, respectively. Both of the DOX loaded liposomes were stable after one month placed at room temperature. Two DOX loaded liposomes showed better anti-cancer effect than free DOX above 5 μg/mL, and they can be internalized into cells and produce more release of DOX inside MCF-7 cells and HepG2 cells at pH 5.0. These results suggested that synthesized lipids are suitable as potential low toxicity cationic drug delivery systems.
Identification and immunological evaluation of novel TLR2 agonists through structure optimization of Pam3CSK4
Du, Xinming,Qian, Jiawen,Wang, Yujie,Zhang, Mingming,Chu, Yiwei,Li, Yingxia
, p. 2784 - 2800 (2019/05/17)
Toll-like receptor 2 (TLR2) is a bridge between innate immunity and adaptive immunity. TLR2 agonists have been exploited as potential vaccine adjuvants and antitumor agents. However, no TLR2 agonists have been approved by FDA up to now. To discover drug-like TLR2 selective agonists, a novel series of Pam3CSK4 derivatives were designed based on the crystal structure of hTLR2-hTLR1-Pam3CSK4 complex, synthesized and evaluated for their immune-stimulatory activities. Among them, 35c was identified as a murine-specific TLR2 agonist, while 35f was a human-specific TLR2 agonist. Besides, 35d (human and murine TLR2 agonist) showed TLR2 agonistic activity comparable to Pam3CSK4, which included: elevated IL-6 expression level (EC50 = 83.08 ± 5.94 nM), up-regulated TNF-α and IL-6 mRNA expression and promoted maturation of DCs through activating the NF-κB signaling pathway. TLRs antibodies test showed that 35a and 35d were TLR2/1 agonists, while 35f was a TLR2/6 agonist.
N-Guanidino Derivatives of 1,5-Dideoxy-1,5-imino-d-xylitol are Potent, Selective, and Stable Inhibitors of β-Glucocerebrosidase
Sev?ek, Alen,?rot, Luka,Rihter, Jakob,?elan, Ma?a,van Ufford, Linda Quarles,Moret, Ed E.,Martin, Nathaniel I.,Pieters, Roland J.
supporting information, p. 483 - 486 (2017/04/10)
A series of lipidated guanidino and urea derivatives of 1,5-dideoxy-1,5-imino-d-xylitol were prepared from d-xylose using a concise synthetic protocol. Inhibition assays with a panel of glycosidases revealed that the guanidino analogues display potent inhibition against human recombinant β-glucocerebrosidase with IC50 values in the low nanomolar range. Related urea analogues of 1,5-dideoxy-1,5-imino-d-xylitol were also synthesized and evaluated in the same fashion and found to be selective for β-galactosidase from bovine liver. No inhibition of human recombinant β-glucocerebrosidase was observed for the urea analogues. Computational studies provided insight into the potent activity of analogues bearing the substituted guanidine moiety in the inhibition of lysosomal glucocerebrosidase (GBA).
Synthesis and characterization of acetylated sept-d-glucopyranose carbamate as an oligosaccharide donor
Lian, Chang-Ming,Jiang, Li-Ping,Liu, Dong-Liang
, p. 134 - 136 (2014/02/14)
An oligosaccharide donor, acetylated sept-d-glucopyranose tetradecyl carbamate, was designed and synthesized. This compound could be easily linked to hydroxyl-containing compounds through an O-glycosidic bond. Characterization of all the oligosaccharide intermediates and the final product was thoroughly discussed.
Semicarbazides as gel forming agents for common solvents and liquid crystals
Deindoerfer, Pia,Geiger, Thomas,Schollmeyer, Dieter,Ye, Jian Hui,Zentel, Rudolf
, p. 351 - 358 (2007/10/03)
This paper describes the synthesis of 14 new gelling agents with semicarbazide groups as H-bonding motifs and alkyl- and/or azobenzene side groups. They gel solvents like decaline, 1,2-dichlorobenzene and toluene and liquid crystalline mixtures. X-Ray structure analysis shows that the semicarbazides are connected by H-bonds, each molecule to four neighbours. As a result a ribbon is formed with a core of H-bonded semicarbazide groups and alkyl chains sticking to the side. IR measurements show an unchanged H-bonding motif in large crystals and in the gel fibres, even in LC-mixture. During heating the gel melts (rheology), while the H-bonding motif of the crystal disappears (IR and DSC measurements). First experiments show that these gel-forming agents can be used to gel LC-phases and to stabilise the director pattern present during gel formation. The Royal Society of Chemistry 2006.
CHIMIE DES SUCRES SANS GROUPEMENTS PROTECTEURS-II REACTIONS SELECTIVES D'ADDITION DU D-GLUCOSE, DU D-GALACTOSE ET DE D-GLYCOSYLAMINES A DES HETEROCUMULENES
Plusquellec, Daniel,Roulleau, Fabienne,Lefeuvre, Martine,Brown, Eric
, p. 465 - 474 (2007/10/02)
Alkyl isocyanates reacted with 1.5 equivalent of α-methylglucoside, glucose or galactose in pyridine at room temperature, and selectively gave the corresponding 6-N-alkylcarbamates in good yields.The readily available glucosylamine and lactosylamine (1.5-2 eq.) reacted with alkyl isocyanates and isothiocyanates in polar aprotic solvents (pyridine, NMP or DMF), thus affording good yields of the corresponding N-glycosyl N'-alkyl ureas and thioureas.These new sugar derivatives are non-ionic detergents.
