4196-95-6Relevant academic research and scientific papers
Bacteria-triggered release of antimicrobial agents
Komnatnyy, Vitaly V.,Chiang, Wen-Chi,Tolker-Nielsen, Tim,Givskov, Michael,Nielsen, Thomas E.
, p. 439 - 441 (2014)
Medical devices employed in healthcare practice are often susceptible to microbial contamination. Pathogenic bacteria may attach themselves to device surfaces of catheters or implants by formation of chemically complex biofilms, which may be the direct cause of device failure. Extracellular bacterial lipases are particularly abundant at sites of infection. Herein it is shown how active or proactive compounds attached to polymeric surfaces using lipase-sensitive linkages, such as fatty acid esters or anhydrides, may be released in response to infection. Proof-of-concept of the responsive material is demonstrated by the bacteria-triggered release of antibiotics to control bacterial populations and signaling molecules to modulate quorum sensing. The self-regulating system provides the basis for the development of device-relevant polymeric materials, which only release antibiotics in dependency of the titer of bacteria surrounding the medical device. Bacteria-responsive materials: A new approach for the construction of antimicrobial polymeric materials is presented. Optimized solid-phase synthesis protocols provide access to drug hybrid constructs with lipase-labile chemical bonds. Upon cleavage of this labile bond by a cognate bacterial lipase, the release of antimicrobial compounds is triggered (see picture).
Design, synthesis, and biological evaluation of HDAC degraders with CRBN E3 ligase ligands
Li, Jia,Lu, Wei,Lu, Yingxin,Shao, Yingying,Su, Mingbo,Sun, Danwen,Xiao, Donghuai,Zhou, Yubo,Zhu, Shulei
, (2021/12/02)
Histone deacetylases (HDACs) play important roles in cell growth, cell differentiation, cell apoptosis, and many other cellular processes. The inhibition of different classes of HDACs has been shown to be closely related to the therapy of cancers and other diseases. In this study, a series of novel CRBN-recruiting HDAC PROTACs were designed and synthesized by linking hydroxamic acid and benzamide with lenalidomide, pomalidomide, and CC-220 through linkers of different lengths and types. One of these PROTACs, denoted 21a, with a new benzyl alcohol linker, exhibited comparably excellent HDAC inhibition activity on different HDAC classes, acceptable degradative activity, and even better in vitro anti-proliferative activities on the MM.1S cell line compared with SAHA. Moreover, we report for the first time the benzyl alcohol linker, which could also offer the potential to be used to develop more types of potent PROTACs for targeting more proteins of interest (POI).
Synthesis of the anti-melanogenic glycerol fatty acid ester isolated from the tuber-barks of colocasia antiquorum var esculenta
Zhu, Shijun,Wu, Yikang
supporting information, p. 261 - 264 (2014/02/14)
(2′S)-1-O-9-Oxo-(10E,12E)-octadecadienoyl glycerol, a natural anti-melanogenic monoglyceride, is synthesized for the first time. The chiral pool based route employed not only confirms the absolute configuration, but also illustrates the first synthetic entry to the (E,E)-diene keto acid, which is another molecule of biological importance. The confusion caused by the misinterpreted 1H NMR spectroscopic data for the (E,E)-diene motif in the literature is discussed. The first unequivocal piece of evidence for the assigned (12E) configuration is also presented. Georg Thieme Verlag Stuttgart, New York.
Novel bioactive phospholipids: Practical total syntheses of products from the oxidation of arachidonic and linoleic esters of 2-lysophosphatidylcholine
Sun, Mingjiang,Deng, Yijun,Batyreva, Eugenia,Sha, Wei,Salomon, Robert G.
, p. 3575 - 3584 (2007/10/03)
Total syntheses of nine novel phospholipids were accomplished to facilitate the identification and biological testing of compounds that are generated upon oxidative cleavage of arachidonate and linoleate esters of 2-lysophosphatidylcholine, the two most abundant polyunsaturated phospholipids in low-density lipoprotein. An efficient general synthesis exploiting 2-lithiofuran as a 4-oxo-2butenoyl carbanion equivalent provided phospholipids containing γ-keto-α,β-unsaturated carbonyl functional arrays. By exploiting facile cis-trans isomerizations, two commercially available cis alkenes, (2Z)-2-butene-1,4-diol and 2,5-dihydrofuran, could be employed as starting materials for preparing the Horner-Wadsworth-Emmons reagent 4-(diethoxyphosphoryl)-2E-butenal, a valuable building block for the synthesis of 2,4-dienals. The reagent was exploited in a total synthesis of 13-oxotridec-9E,11E-dienoic acid, confirming the identity of this product that is generated upon autoxidation of linoleic acid and by decomposition of 13-hydroperoxy-9,11-octadecadienoate (13HPODE), especially in the presence of redox active transition metal ions, cytochrome p-450, or hydroperoxide lyase.
