5845-61-4Relevant articles and documents
En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal-Organic Framework Catalysts
Conic, Dragan,De Azambuja, Francisco,Harvey, Jeremy N.,Loosen, Alexandra,Parac-Vogt, Tatjana N.,Van Den Besselaar, Maxime
, p. 7647 - 7658 (2021/06/30)
Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis is key to circumvent current bottlenecks. To date, many homogeneous catalysts able to provide synthetically useful methods have been developed, while heterogeneous catalysts remain largely restricted to the studies addressing the prebiotic formation of peptides. Here, the catalytic activity of Zr6-based metal-organic frameworks (Zr-MOFs) toward peptide bond formation is investigated using dipeptide cyclization as a model reaction. Unlike previous catalysts, Zr-MOFs largely tolerate water, and reactions are carried out under ambient conditions. Notably, the catalyst is recyclable and no additives to activate the COOH group are necessary, which are common limitations of previous methods. In addition, a broad reaction scope tolerates substrates with bulky and Lewis basic groups. The reaction mechanism was assessed by detailed mechanistic and computational studies and features a Lewis acid activation of carboxylate groups by Zr centers toward amine addition in which an alkoxy ligand on adjacent Zr sites assists in lowering the barrier of key proton transfers. The proposed concepts were also used to study the formation of intermolecular peptide bond formation. While intrinsic challenges associated with the catalyst structure and water removal limit a more general intermolecular reaction scope under current conditions, the results suggest that further design of Zr-MOF catalysts could render these materials broadly useful as heterogeneous catalysts for this challenging transformation.
Design, synthesis and antitumor activity evaluation of Chrysamide B derivatives
Zhu, Longqing,Li, Junfang,Fan, Xiaohong,Hu, Xiaoling,Chen, Jinhong,Liu, Yonghong,Hao, Xiangyong,Shi, Tao,Wang, Zhen,Zhao, Quanyi
, (2021/04/29)
Marine natural products derived from special or extreme environment provide an important source for the development of anti-tumor drugs due to their special skeletons and functional groups. In this study, based on our previous work on the total synthesis and structure revision of the novel marine natural product Chrysamide B, a group of its derivatives were designed, synthesized, and subsequently of which the anti-cancer activity, structure-activity relationships and cellular mechanism were explored for the first time. Compared with Chrysamide B, better anti-cancer performance of some derivatives against five human cancer cell lines (SGC-7901, MGC-803, HepG2, HCT-116, MCF-7) was observed, especially for compound b-9 on MGC-803 and SGC-7901 cells with the IC 50 values of 7.88 ± 0.81 and 10.08 ± 1.08 μM, respectively. Subsequently, cellular mechanism study suggested that compound b-9 treatment could inhibit the cellular proliferation, reduce the migration and invasion ability of cells, and induce mitochondrial-dependent apoptosis in gastric cancer MGC-803 and SGC-7901 cells. Furthermore, the mitochondrial-dependent apoptosis induced by compound b-9 is related with the JAK2/STAT3/Bcl-2 signaling pathway. To conclude, our results offer a new structure for the discovery of anti-tumor lead compounds from marine natural products.
Discovery of a novel inhibitor of nitric oxide production with potential therapeutic effect on acute inflammation
Zhu, Long-Qing,Fan, Xiao-Hong,Li, Jun-Fang,Chen, Jin-Hong,Liang, Yan,Hu, Xiao-Ling,Ma, Shu-Meng,Hao, Xiang-Yong,Shi, Tao,Wang, Zhen
supporting information, (2021/05/26)
Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure–activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC50 = 0.010 μM) and the activity of iNOS (IC50 = 0.082 μM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future.
Novel piperazine compound as well as preparation method and application thereof
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Paragraph 0078-0080; 0084-0085, (2020/04/22)
The structural general formula of a novel piperazine compound is shown in the specification. The invention aims to provide a novel anti-inflammatory drug with high efficiency and low side effect. Because typical marine characteristic skeleton molecules ri
Chrysamide B derivative with anti-tumor activity and preparation and application of Chrysamide B derivative
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Paragraph 0061-0063; 0065, (2020/08/02)
The invention belongs to the field of medicinal chemistry, and particularly relates to a marine natural product Chrysamide B and a derivative thereof. The marine natural product Chrysamide B comprisesstereoisomers or pharmaceutically acceptable salts, solvates and prodrugs of the marine natural product Chrysamide B, general formulas are shown in a formula (I), a formula (II) and a formula (III).The invention also provides preparation and application of the compound. The compound has an anti-cancer effect; the compound has good inhibitory activity on digestive system cancers, leukemia, livertumors, non-small cell lung cancers, cervical cancers, breast cancers and the like and has the effects of inducing tumor cell apoptosis, activating apoptosis protein expression, retarding cycle, inhibiting proliferation and the like and is a potential antitumor drug.
Investigation of permeation of theophylline through skin using selected piperazine-2,5-diones
Pokorna, Aneta,Bobal, Pavel,Oravec, Michal,Rarova, Lucie,Bobalova, Janette,Jampilek, Josef
, (2019/02/26)
Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 ?C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.
Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens
Simon, Ga?lle,Bérubé, Christopher,Voyer, Normand,Grenier, Daniel
, p. 2323 - 2331 (2018/12/11)
Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure–activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms.
Synthesis method for nitro group-containing natural product chrysamides B and diastereoisomer-compound thereof
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Paragraph 0042; 0043, (2018/11/22)
The invention belongs to the technical fields of medicinal chemistry and organic synthesis, and relates to a synthesis method for a nitro group-containing natural product chrysamides B, a chrysamidesB diastereoisomer-compound and a synthesis method and application thereof. According to the invention, a convergent synthesis method is adopted to condense chiral epoxy carboxylic acid and chiral dimethylpiperazine ring, and thereby the nitro group-containing natural product chrysamides B with a symmetrical structure and the chrysamides B diastereoisomer-compound are easily and efficiently synthesized. By three-step continuous oxidation, chiral epoxy carboxylic acid is prepared from p-nitrobenzaldehyde which is easy to obtain commercially, and dimethylpiperazine ring is prepared by reduction after alanine dimerization. The compound shows inhibitory activity on pasteurella multocida. Such a convergent synthesis route can be applied to the chemical synthesis of compounds with the similar structure and related derivatives, opening up a broad development space for novel antibiotic drugs.
Interfacial supramolecular biomimetic epoxidation catalysed by cyclic dipeptides
Bérubé, Christopher,Barbeau, Xavier,Cardinal, Sébastien,Boudreault, Pierre-Luc,Bouchard, Corinne,Delcey, Nicolas,Lagüe, Patrick,Voyer, Normand
, p. 330 - 349 (2017/03/15)
We synthesised a library of cis- and trans-cyclic dipeptides and evaluated their efficacy as catalysts in the asymmetric Weitz-Scheffer epoxidation of trans-chalcone. A thorough investigation relying on structure-activity studies and computational studies provided insights into the mechanism of the process. Our results revealed some structural features required for efficient conversion and for introduction of chirality into the product. The cyclic dipeptide acts as a catalyst by templating a supramolecular arrangement at the aqueous-organic interface required for efficient transformations to occur. Among all cyclic dipeptides investigated, cyclo(Leu-Leu) was the most efficient supramolecular catalyst.
AGRICULTURAL CHEMICAL CONTAINING 2,5-DIKETOPIPERAZINE DERIVATIVE AS ACTIVE INGREDIENT
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Paragraph 0033, (2013/06/05)
Disclosed herein is an agricultural agent containing a 2,5-diketopiperazine derivative capable of controlling plant diseases and promoting plant growth or an agriculturally acceptable salt thereof as an active ingredient.
