13139-14-5Relevant articles and documents
Synthesis and biological evaluation of novel 1-Alkyl-tryptophan analogs as potential antitumor agents
Sun, Ting,Li, Zhao-Long,Tian, Hua,Wang, Shih-Chen,Cai, Jiong
, p. 5339 - 5348 (2009)
To seek novel antitumor agents, we designed and synthesized new 1-tryptophan analogs based on tryptophan catabolism. 1-Alkyl-tryptophan analogues including 1-ethyl-tryptophan (1-ET), 1-propyltryptophan (1-PT), 1-isopropyltryptophan (1-isoPT) and 1-butyltryptophan (1-BT) were synthesized from tryptophan. We examined whether those compounds had the antiproliferative effects on SGC7901 and HeLa cells line by using MTT assay in vitro, respectively. Compared to tryptophan, all targeted compounds efficiently inhibited proliferation of two cancer cell lines at 2 mmol/L for 48 hours. Among these tryptophan analogs, 1-BT showed the most powerful cytotoxicity against SGC7901 and HeLa cells at 1 mmol/L and 2 mmol/L concentration. These data suggest that some specific tryptophan analogs could be developed as potential anti-neoplastic agents.
Soluble non-cross-linked poly(norbornene) supports for peptide synthesis with minimal reagents
Naganna, Nimmashetti,Madhavan, Nandita
, p. 11549 - 11557 (2014)
Solid-phase peptide synthesis has been an attractive method for synthesizing peptides because it is quick and can be automated. The heterogeneous reaction medium in solid-phase peptide synthesis necessitates the use of large equivalents of reagents to drive the reactions to completion. Peptide synthesis using soluble, yet isolable, supports is an attractive alternative to solid-phase peptide synthesis. Reported herein is a soluble poly(norbornene)-derived support containing multiple attachment sites for high loading capacities and solubilizing oligoether/alkyl groups. The Ala-attached support has been used to synthesize tri- to octapeptides in 28 to 97% yields using only 1.2 equiv of amino acids and coupling reagents. The acyclic hexapeptide precursor to natural product segatalin A was synthesized in 41% yield on the support using one-eighth of the equivalents of coupling reagents compared to that in reported procedures. The support could be recovered in up to 98% yield after peptide synthesis, and the recovered support was utilized to synthesize tri- and tetrapeptides that contain amino acids other than Ala at the C-terminus in ca. 80% yields.
Lead discovery of a guanidinyl tryptophan derivative on amyloid cascade inhibition
Jiaranaikulwanitch, Jutamas,Suwanttananuruk, Piyapan,Vajragupta, Opa,Waiwut, Pornthip
, p. 546 - 558 (2020)
Amyloid cascade, one of pathogenic pathways of Alzheimer's disease (AD), was focused as one of drug discovery targets. In this study, β-secretase (BACE1) inhibitors were designed aiming at the development of multifunctional compounds targeting amyloid pathogenic cascade. Tryptophan was used as a core structure due to its properties of the central nervous system (CNS) penetration and BACE1 inhibition activity. Three amino acid residues and guanidine were selected as linkers to connect the tryptophan core structure and the extended aromatic moieties. The distance between the aromatic systems of the core structure and the extended moieties was kept at the optimal length for amyloid-β (Aβ) peptide binding to inhibit its fibrillation and aggregation. Sixteen designed compounds were evaluated in silico. Eight hit compounds of TSR and TGN series containing serine and guanidine linkers, respectively, were identified and synthesized based on docking results. TSR2 and TGN2 were found to exert strong actions as BACE1 (IC50 24.18 μM and 22.35 μM) and amyloid aggregation inhibitors (IC50 37.06 μM and 36.12 μM). Only TGN2 demonstrated a neuroprotective effect in SH-SY5Y cells by significantly reducing Aβ-induced cell death at a concentration of 2.62 μM. These results support the validity of multifunctional approaches to inhibition of the β-amyloid cascade.
Conditional changes enhanced production of bioactive metabolites of marine derived fungus Eurotium rubrum
Kamauchi, Hitoshi,Kinoshita, Kaoru,Sugita, Takashi,Koyama, Kiyotaka
, p. 4911 - 4914 (2016)
Metabolites of marine derived fungus Eurotium rubrum MPUC136 differed between cultivation on wheat medium and Czapek-Dox agar medium. Melanin synthesis inhibitory activity of crude extract of culture on wheat medium showed stronger activity than that of crude extract of culture on Czapek-Dox agar medium. A new diketopiperazine compound isoechinulin D (1) and eight reported diketopiperazines (2–9) were isolated from the crude extract of wheat medium. The structure of 1 was established using NMR, MS and IR methods. 2–5 inhibited melanogenesis using B16 melanoma cells (IC50?=?68, 2.4, 83, 9.1?μM each). Structure–Activity-Relationships of diketopiperazines (1–10) indicated the importance of the prenyl groups at C-2, C-5 and C-7, the vinyl group at C-12 to C-25 and the sp2carbons at C-8 and C-9. Isolated compounds (1–9) were not or slightly observed from the extracts of Czapek-Dox agar medium by HPLC analysis, suggesting that different cultivation processes could affect metabolism and enhance bioactivities.
L-Proline induced self-assembly of indolicidin derived palindromic tripeptide
Joshi, Khashti Ballabh,Singh, Prabhpreet
, p. 3534 - 3537 (2014)
We describe the synthesis, crystal structure, and various microscopic studies of the palindromic tripeptide WPW derived from antimicrobial peptide indolicidin. The present study reveals that tripeptide 1 and 2 undergo self-assembly to form vesicular structures after prolonged incubation, thus giving an interesting insight into the contribution of l-proline and flanking tryptophan residues in the self-assembly process. These vesicles were also amenable to simple focused ion beam (FIB)-aided bisection and thus possible to mill these vesicles to create different shapes. The circular dichroism (CD) analysis indicates that incubation promotes and stabilizes the more favorable secondary structures for 1 and 2. Preliminary result shows that tripeptide 1 exhibits appreciable interaction with Tb3+ as determined by quenching in tryptophan fluorescence.
Amino acid derivatives, IX [1]: Synthesis and antimicrobial evaluation of α-amino acid esters bearing a tryptophane side chain
Hameurlaine, Ahmed,El-Sayed, Wael A.,Abdel-Rahman, Adel A.-H.
, p. 1507 - 1511 (2008)
A series of peptide and dipeptide derivatives conjugated with a tryptophane residue were synthesized. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.
Design and synthesis of enantiopure 18F-labelled [18F]trifluoromethyltryptophan from 2-halotryptophan derivatives via copper(I)-mediated [18F]trifluoromethylation and evaluation of its in vitro characterization for the serotonergic system imaging
Kim, Ho Young,Lee, Ji Youn,Lee, Yun-Sang,Jeong, Jae Min
, p. 566 - 579 (2019)
We synthesized [18F]trifluoromethyl-l-tryptophan ([18F]CF3-l-Trp) using Cu(I)-mediated [18F]trifluoromethylation to image serotonergic system. Radiochemical yield was 6 ± 1.5% (n = 9), and radiochemical purity was over 99%. The molar activity was 0.44 to 0.76 GBq/μmol. [18F]CF3-l-Trp was stable for up to 6 hours in mouse and human sera at 37°C. Protein-binding was 0.26 ± 0.03% and 0.34 ± 0.02% in human and mouse serum at 60 minutes, respectively. In conclusion, enantiopure [18F]CF3-l-Trp was synthesized as a feasible imaging agent for the serotonergic system.
Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor**
Sardar, Avijit,Lahiri, Aritraa,Kamble, Mithila,Mallick, Amirul I.,Tarafdar, Pradip K.
supporting information, p. 6101 - 6106 (2021/02/01)
The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome–lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
, p. 292 - 297 (2020/04/21)
Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
SMALL-MOLECULAR ADJUVANTS AND IMPLEMENTATIONS THEREOF
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Paragraph 0090; 0092; 00117, (2020/10/27)
The present disclosure describes compounds of the general Formula (I) or its stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates, hydrates, thereof. These compounds or small molecular adjuvants in combination with antibiotics are effective against resistant bacterial infections. The present disclosure also discloses a process of preparation of small-molecular adjuvants, its stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof, and to pharmaceutical compositions containing them
