94888-34-3Relevant academic research and scientific papers
Rational design of bacitracin A derivatives by incorporating natural product derived heterocycles
Wagner, Bjoern,Schumann, Dirk,Linne, Uwe,Koert, Ulrich,Marahiel, Mohamed A.
, p. 10513 - 10520 (2006)
Heterocycles display common structural motifs in nonribosomally produced peptides with an enormous impact on their bioactivity. In the case of the branched cyclic Bacitracin A, the thiazoline moiety is manufactured during NRPS peptide chain elongation. Here we describe a method to selectively alter the heterocyclic metal binding subunit of Bacitracin A by the synthesis of heterocyclic building blocks that were successfully coupled to the linear decapeptide and subsequently cyclized using the excised bacitracin PCP-TE bidomain. Utilization of this cyclase allowed the first generation of branched cyclic bacitracin derivatives containing thiazole and oxazoles. The generated bacitracin derivatives showed bactericidal activity, indicating the possibility of altering the biological important heterocyclic subunit and overcoming existing limitations for the application of bacitracin.
Design, synthesis and anxiolytic activity evaluation of N-Acyltryptophanyl- containing dipeptides, potential TSPO ligands
Deeva, Olga A.,Dyabina, Alina S.,Gudasheva, Tatiana A.,Mokrov, Grigory V.,Seredenin, Sergey B.,Yarkova, Milada A.
, p. 383 - 399 (2019/07/12)
Background: The 18 kDa translocator protein (TSPO), previously known as the peripheral- type benzodiazepine receptor, plays a key role for the synthesis of neurosteroids by promoting transport of cholesterol from the outer to the inner mitochondrial membrane, which is the ratelimiting step in neurosteroid biosynthesis. Neurosteroids interact with nonbenzodiazepine site of GABAa receptor causing an anxiolytic effect without the side effects. Methods: Using the original peptide drug-based design strategy, the first putative dipeptide ligand of the TSPO N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23) was obtained. Molecular docking of GD-23 in the active pocket of the TSPO receptor using Glide software was carried out. The lead compounds GD-23 and its analogues were synthesized using activated succinimide esters coupling method. The anxiolytic activity of GD-23 and its analogues was investigated in vivo, using two validated behavioral tests, illuminated open field and elevated plus-maze. Results: The in vivo studies revealed that the following parameters are necessary for the manifestation of anxiolytic activity of new compounds: the L-configuration of tryptophan, the presence of an amide group at the C-terminus, the specific size of the N-acyl substituent at the Nterminus. Compound GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide) demonstrated a high anxiolytic-like effect in the doses of 0.05-1.0 mg/kg i.p. comparable with that of diazepam. Compound GD-23 was also active in the open field test when was administered orally in the doses of 0.1-5.0 mg/kg. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by the antagonism of compound GD-23 with TSPO selective inhibitor PK11195 as well as with inhibitors of enzymes which are involved in the biosynthesis of neurosteroids, trilostane and finasteride. Conclusion: A series of N-acyl-tryptophanyl-containing dipeptides were designed and synthesized as 18 kDa translocator protein (TSPO) ligands. Using a drug-based peptide design method a series of the first dipeptide TSPO ligands have been designed and synthesized and their anxiolytic activity has been evaluated. In general, some of the compounds displayed a high level of anxiolytic efficacy comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic activity of new compounds was proved using two methods. On this basis, the N-acyl-Ltryptophanyl- isoleucine amides could potentially be a novel class of TSPO ligands with anxiolytic activity.
Total synthesis, structure, and oral absorption of a thiazole cyclic peptide, sanguinamide A
Nielsen, Daniel S.,Hoang, Huy N.,Lohman, Rink-Jan,Diness, Frederik,Fairlie, David P.
supporting information, p. 5720 - 5723 (2013/01/15)
The first total synthesis and three-dimensional solution structure are reported for sanguinamide A, a thiazole-containing cyclic peptide from the sea slug H. sanguineus. Solution phase fragment synthesis, solid phase fragment assembly, and solution macroc
Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects
Chen, Shi-Wu,Gao, Yuan-Yu,Zhou, Ni-Ni,Liu, Jie,Huang, Wen-Ting,Hui, Ling,Jin, Yan,Jin, Yong-Xin
supporting information; experimental part, p. 7355 - 7358 (2012/02/04)
In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4′-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4′-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4′- demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.
Isoselenocyanates derived from Boc/Z-amino acids: Synthesis, isolation, characterization, and application to the efficient synthesis of unsymmetrical selenoureas and selenoureidopeptidomimetics
Chennakrishnareddy, Gundala,Nagendra, Govindappa,Hemantha, Hosahalli P.,Das, Ushati,Guru Row, Tayur N.,Sureshbabu, Vommina V.
supporting information; experimental part, p. 6718 - 6724 (2010/09/30)
Isoselenocyanates derived from Boc/Z-amino acids are prepared by the reaction of the corresponding isonitriles with selenium powder in presence of triethylamine at reflux. The utility of these new classes of isoselenocyanates in the preparation of selenoureidodipeptidomimetics possessing both amino as well as carboxy termini has been accomplished. The 1H NMR analysis confirmed that the protocol involving the conversion of isonitriles to isoselenocyanates and their use as coupling agents in assembling selenoureido derivatives is free from racemization.
Synthesis of Boc-amino tetrazoles derived from α-amino acids
Sureshbabu, Vommina V.,Naik, Shankar A.,Nagendra
experimental part, p. 395 - 406 (2009/06/06)
A simple route for the synthesis of Boc-protected tetrazole analogs of amino acids starting from Nα-Boc amino acids has been described. The [2 + 3] cycloaddition of Boc-α-amino nitrile and sodium azide in the presence of a catalytic amount of zinc bromide yielded the desired tetrazoles in good yields and purity. All the compounds obtained have been characterized by 1H and 13C-NMR and mass spectral studies. Copyright Taylor & Francis Group, LLC.
Total synthesis of the cyclopeptide alkaloid paliurine E. insights into macrocyclization by ene-enamide RCM
Toumi, Mathieu,Couty, Francois,Evano, Gwilherm
, p. 1270 - 1281 (2008/09/16)
(Chemical Equation Presented) The total synthesis of (-)-paliurine E is described in 14 steps and 11% overall yield. The first successful application of ene-enamide ring-closing metathesis for macrocyclization serves as the foundation for this synthesis a
Control of competing N-H insertion and Wolff rearrangement in dirhodium(II)-catalyzed reactions of 3-indolyl diazoketoesters. Synthesis of a potential precursor to the marine 5-(3-indolyl)oxazole martefragin A
Davies, James R.,Kane, Peter D.,Moody, Christopher J.,Slawin, Alexandra M. Z.
, p. 5840 - 5851 (2007/10/03)
Dirhodium(II)-catalyzed reaction of 3-indolyl α-diazo-β- ketoester 25 in the presence of hexanamide results in competing metal carbene N-H insertion and Wolff rearrangement. The corresponding phenyl diazoketoester 32, on the other hand, gives only the product of N-H insertion, suggesting that the indole moiety is more prone to 1,2-rearrangement. The competing processes were investigated in a range of 3-indolyl α-diazo-β-ketoesters (36, 38, 40, 44); these studies established that the Wolff rearrangement could be effectively suppressed by the presence of a strong electron-withdrawing group on the indole nitrogen. Dirhodium(II) catalysts were also more effective than copper or Lewis acid catalysts in favoring the insertion process. The products of N-H insertion, the ketoamides (26, 47, 49, 51, 53), were readily cyclodehydrated to the corresponding 5-(3-indolyl)-oxazoles. The N-H insertion/cyclodehydration methodology was used in a formal synthesis of the marine natural product martefragin A. Thus the N-Boc homoisoleucine amide 23, prepared by asymmetric hydrogenation of a dehydro amino acid, underwent N-H insertion with the rhodium carbene derived from the N-nosyl indolyl diazoester 40, followed by cyclodehydration and deprotection to give the 5-(3-indolyl)oxazole martefragin A precursor 75.
Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics
Leite, Ana Cristina L.,Vieira, Renata F.,De Faria, Antonio R.,Wanderley, Almir G.,Afiatpour, Parviz,Ximenes, Eulalia Camelo P. A.,Srivastava, Rajendra M.,De Oliveira, Claudia F.,Medeiros,Antunes, Edson,Brondani, Dalci J.
, p. 719 - 724 (2007/10/03)
A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the
Convenient Synthesis of N-Protected Amino Acid Amides
Nozaki, Sukekatsu,Muramatsu, Ichiro
, p. 2647 - 2648 (2007/10/02)
Boc- or Z-amino acids were conveniently amidated at room temperature by a one-pot procedure employing ammonium hydrogencarbonate and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in yields of 81-96percent.The benzyl ester-type protector for the side chains of aspartic acid and glutamic acid was not affected by the procedure.
