Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• natural substrate for sialidases and its chemical modification has been a useful approach to generate potent and selective inhibitors. Aiming at advancing the discovery of selective Trypanosoma cruzi trans-sialidase (TcTS) inhibitors, we have synthesised a small series of anomeric 1,2,3-triazole-linked

• protozoa sialidases remain a big challenge. An important example relates to Trypanosoma cruzi trans-sialidase (TcTS), which plays a central role in the infection process and modulation of the host immune response in Chagas disease. Anchored to the protozoan parasite surface, TcTS transfers terminal sialic

• pentaerythritol homoglycocluster reported by the Carvalho group [17] and a C-sialoside bearing phenylpropyl group at C-2 [18] (Figure 1C). In the context of mimicking the terminal sugars α-ᴅ-Neu5Ac(2,3)-β-ᴅ-Gal of Trypanosoma cruzi mucins to obtain potent TcTS inhibitors, our group previously synthesised a small

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• subtilis, giving a MIC of 3.1 µg/mL [87]. 42 displayed in vitro antiparasitic activity against Plasmodium falciparum (K1, NF54), Leshmania donovani, Trypanosoma cruzi and T. rhodesiense but the effect was much lower than that of standard drugs artemisinin and chloroquine [88]. Ascididemin (42) displayed

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• . The Ellman group demonstrates the power of their chiral sulfinylimine protocol to synthesize propargylamine-derived alpha-tetrasubstituted triazoles (tetrasubstituted carbon bearing amine highlighted in red, Figure 1). One such triazole is a cruzain inhibitor with activity against parasite Trypanosoma

• cruzi, which causes Chagas’ disease [6]. An alpha-tetrasubstituted triazole that inhibits cathepsin S can potentially treat ailments ranging from inflammation to autoimmune disorders [7][8]. The core of the cathepsin S inhibitor is synthesized in six steps. Synthesis and isolation of an N-sulfinyl

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• divalent β-N- and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp

• . Keywords: β-galactopyranosides; multivalent ligands; sialic acid; sugar scaffolds; T. cruzi trans-sialidase; Introduction Trypanosoma cruzi, the agent of American trypanosomiasis, affects millions of people in Latin America [1][2] and is transmitted to animals, including humans, by triatomine insects. The

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• trans-sialidase (TcTS) [48], a virulence factor of Trypanosoma cruzi [49][50][51]. It was shown that lactitol prevented apoptosis caused by TcTS although it is rapidly eliminated from the circulatory system [52]. With the aim to improve bioavailability, PEGylation of lactose analogs was performed using

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• , 1700 4th Street, San Francisco, CA, 94158, USA Cellular Ultra-Structure Laboratory, Oswaldo Cruz Institute (IOC), FIOCRUZ, Rio de Janeiro, RJ, Brazil 21040-362 10.3762/bjoc.9.3 Abstract Inhibition of the Trypanosoma cruzi cysteine protease cruzain has been proposed as a therapeutic approach for the

• of this new class of inhibitors. Keywords: activity-based probes; Chagas’ disease; cruzain; CYP51; 14-α-demethylase; hybrid drugs; Trypanosoma cruzi; Introduction The kinetoplastid protozoan Trypanosoma cruzi is the causative agent of Chagas’ disease, a leading cause of heart failure in endemic

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• activity was detected. Additionally, the peptide 1 was tested against several parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, Plasmodium falciparum) being the causative agents of the neglected tropical diseases [18] sleeping sickness, leishmaniasis and malaria

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• has been reported in which sialylation with recombinant transsialidase (Trypanosoma cruzi) gave the trisaccharide 3 in 32% yield [8]. Treatment of 3 with methanol and acidic ion exchange resin led to the methyl ester (for the method cf. lit. [9]) which was then peracetylated to give trisaccharide 4 as