- Design, Synthesis and Biological Evaluation of Bengamide Analogues as ClpP Activators
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To combat multidrug-resistant Gram-positive bacteria, new antimicrobials particularly those with novel mechanism of action are badly needed. Different with conventional antibiotics which are typical inhibitors, small-molecule activators of bacterial ClpP represent a new class of antibiotics. No ClpP activator has been developed for clinical trial. Herein, we conducted a screening on our library of bengamide-like ring-opened analogues and found that L472-2 possesses a low minimum inhibitory concentration (MIC) against S.aureus and shows no activity for ClpP activation in vitro, but it displayed reduced antibacterial activity against S. aureus with clpP deletion. In order to obtain bengamide analogues that activate ClpP in vitro as well as possess antibacterial activity, we perform further structural modifications starting from L472-2. Compound 37 remains the antimicrobial activity and activation of ClpP protein in vitro, which could be viewed as a new chemical scaffold for ClpP activators and worthy of further investigation.
- Kong, Xue-Qing,Wei, Bing-Yan,Yu, Chen-Xi,Guan, Xiang-Na,Ma, Wei-Ping,Liu, Gang,Yang, Cai-Guang,Nan, Fa-Jun
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Read Online
- Eco-friendly synthesis of peptides using fmoc-amino acid chlorides as coupling agent under biphasic condition
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Background: Agro-waste derived solvent media act as a greener process for the peptide bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added ad-vantages such as neutralization of amino acid ester salt and not required additional base for the neu-tralization, and directly coupling take place with Fmoc-amino acid chloride gave final product dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead of using inorganic base. Objective: To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid chloride with amino acid esters salt. Methods: The final product isolated is analyzed in several spectroscopic and analytical techniques such as FT-IR,1H-,13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and puri-ty of the product. Conclusion: The present method developed greener using natural agro-waste (lemon fruit shell ash) derived solvent medium for the reaction and not required chemical entity.
- Kantharaju, Kamanna,Khatavi, Santosh Y.
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p. 699 - 707
(2021/08/23)
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- N-transfer reagent and method for preparing the same and its application
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Provided are a novel N-transfer reagent and a method for preparing the same and its application. The N-transfer reagent is represented by the following Formula (I): The various novel N-transfer reagents of the present invention can be quickly prepared by employing different nitrobenzene precursors. The N-transfer reagents can directly convert a variety of amino compounds into diazo compounds under mild conditions. Particularly, the N-transfer reagents can facilitate the synthesis of the diazo compounds. The application of synthesizing diazo compounds of the present invention can greatly decrease the difficulty in operation, increase the safety during experiments, reduce the cost of production and the environmental pollution, and enhance the industrial value of diazo compounds.
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Page/Page column 24; 49-50; 53-54
(2021/06/25)
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- NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds
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A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).
- Lu, Guan-Han,Huang, Tzu-Chia,Hsueh, Hsiao-Chin,Yang, Shin-Cherng,Cho, Ting-Wei,Chou, Ho-Hsuan
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supporting information
p. 4839 - 4842
(2021/05/25)
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- COMPOSITIONS AND METHODS OF USING THE COMPOSITIONS FOR PLAQUE SOFTENING
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Disclosed herein is a compound for use in a composition applied to a blood vessel, wherein the compound softens and/or disrupts the crystalline matrix of calcified plaque. Methods of treatment comprising applying the disclosed composition are also disclosed. Plaque-softening compounds are also disclosed.
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Paragraph 0246; 0247; 0248; 0249
(2014/02/16)
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- Synthesis and insecticidal activity of nitenpyram analogs with tetrahydropyrimidine fixed (z)-configuration
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Two series of novel (Z)-nitenpyram analogs 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 3a, 3b, 3c, 3d were synthesized by introducing various amino acids benzyl ester or amino acids tetrahydrofurfur-2-yl ester into nitenpyram and forming a tetrahydropyrimidine ring to fix (Z)-configuration. The structures of the target compounds were characterized by 1HNMR, MS, IR, and elemental analysis. Preliminary bioassays against Nilaparvata lugens indicated that all the nitenpyram analogs exhibited good insecticidal activity at 100 mg/L, whereas the compounds 3b and 3d afforded the best in vitro inhibitory activities that had ≥ 90% mortality at 20 mg/L.
- Sun, Chuan-Wen,Fang, Ting,Hao, Zhi-Bing,Pang, Chun-Cheng,Xu, Xiao,Xin, Hua-Jia
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p. 1025 - 1030
(2013/10/21)
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- Studies toward novel peptidomimetic inhibitors of thioredoxin-thioredoxin reductase system
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Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-κB and AP-1 and decreases H2O2 scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.
- K?ossowski, Szymon,Muchowicz, Angelika,Firczuk, Ma?gorzata,?wiech, Marta,Redzej, Adam,Golab, Jakub,Ostaszewski, Ryszard
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scheme or table
p. 55 - 67
(2012/02/15)
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- A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis
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Based on DOCK scores 18 N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (6a-r) were synthesized as anti-tumor agents. Their IC 50 values against five human carcinoma cell lines ranged from 11.1 μM to more than 100 μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (6a-r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue.
- Wu, Jianhui,Li, Chunyu,Zhao, Ming,Wang, Wenjing,Wang, Yuji,Peng, Shiqi
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experimental part
p. 6220 - 6229
(2010/10/04)
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- Antiviral phosphoramidates
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The invention provides novel nucleoside compounds of formula I wherein R1, R2a, R2b, R3, R4, R5, R6, R8a, R9 and R10 are as defined herein which are useful for the treatment of Hepatitis C Virus (HCV) mediated diseases. The invention further provides methods for treatment or prophylaxis of HCV mediated diseases with compounds of formula I and pharmaceutical compositions comprising these compounds,
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Page/Page column 18
(2008/06/13)
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- Vertebrate collagenase inhibitor. II. Tetrapeptidyl hydroxamic acids
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To develop a potent and specific collagenase inhibitor, a series of tetrapeptidyl hydroxamic acids were synthesized, based on the previous findings with tripeptidyl derivatives (Chem. Pharm. Bull., 38, 1007-1011, 1990). Among the series of tetrapeptidyl d
- Odake,Okayama,Obata,Morikawa,Hattori,Hori,Nagai
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p. 1489 - 1494
(2007/10/02)
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