scholarly journals Design, Synthesis, and Biological Evaluation of Desmuramyl Dipeptides Modified by Adamantyl-1,2,3-triazole

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6352
Author(s):  
Vesna Petrović Peroković ◽  
Željka Car ◽  
Josip Draženović ◽  
Ranko Stojković ◽  
Lidija Milković ◽  
...  
Keyword(s):  
Immune Response ◽  
Murine Model ◽  
Structural Modification ◽  
Muramyl Dipeptide ◽  
Biological Evaluation ◽  
Adjuvant Activity ◽  
Design Synthesis ◽  
C Terminus ◽  
Synthesis And Biological Evaluation

Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity.

scholarly journals Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

2019 ◽  
Vol 15 ◽  
pp. 1805-1814 ◽  
Author(s):  
Rosana Ribić ◽  
Ranko Stojković ◽  
Lidija Milković ◽  
Mariastefania Antica ◽  
Marko Cigler ◽  
...  
Keyword(s):  
Muramyl Dipeptide ◽  
Biological Evaluation ◽  
Adjuvant Activity ◽  
Design Synthesis ◽  
C Terminus ◽  
Minimal Structure ◽  
Dipeptide Analogues ◽  
Peptide Derivatives ◽  
Mannose Receptors ◽  
Synthesis And Biological Evaluation

Muramyl dipeptide is the minimal structure of peptidoglycan with adjuvant properties. Replacement of the N-acetylmuramyl moiety and increase of lipophilicity are important approaches in the preparation of muramyl dipeptide analogues with improved pharmacological properties. Mannose receptors present on immunocompetent cells are pattern-recognition receptors and by mannose ligands binding they affect the immune system. Here we present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were investigated in the mouse model using ovalbumin as an antigen. Their activities were compared to the previously described mannosylated adamantane-containing desmuramyl peptide and peptidoglycan monomer. Tested compounds exhibited adjuvant activity and the strongest enhancement of IgG production was stimulated by compound 21 (Man-OCH2-ᴅ-(1-Ad)Gly-ʟ-Ala-ᴅ-isoGln).

scholarly journals Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

2019 ◽  
Author(s):  
Rosana Ribić ◽  
Ranko Stojković ◽  
Lidija Milković ◽  
Mariastefania Antica ◽  
Marko Cigler ◽  
...  
Keyword(s):  
Muramyl Dipeptide ◽  
Biological Evaluation ◽  
Adjuvant Activity ◽  
Design Synthesis ◽  
C Terminus ◽  
Minimal Structure ◽  
Dipeptide Analogues ◽  
Peptide Derivatives ◽  
Present Design ◽  
Synthesis And Biological Evaluation

Muramyl dipeptide is the minimal structure of peptidoglycan with adjuvant properties. Replacement of the N-acetylmuramyl moiety and increase of lipophilicity are important approaches in the preparation of muramyl dipeptide analogues with improved pharmacological properties. Mannose receptors present on immunocompetent cells are pattern-recognition receptors and by mannose ligands binding they affect the immune system. Here we present design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptide containing lipophilic adamantane on N- or C-terminus through glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were investigated in the mouse model using ovalbumin as an antigen. Their activities were compared to the previously described mannosylated adamantane-containing desmuramyl peptide and peptidoglycan monomer. Tested compounds exhibited adjuvant activity and the strongest enhancement of IgG production was stimulated by the compound 21 (Man-OCH2-D-(1-Ad)Gly-L-Ala-D-isoGln).

scholarly journals Design, synthesis and biological evaluation of a new bridged immunosuppressor.

2001 ◽  
Vol 48 (4) ◽  
pp. 1147-1150 ◽  
Author(s):  
Z Szewczuk ◽  
A Wilczyński ◽  
I Petry ◽  
I Z Siemion ◽  
Z Wieczorek
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Discontinuous Epitope ◽  
Humoral Immune ◽  
Hla Dq ◽  
Synthesis And Biological Evaluation

A bridged peptide with the sequence: H-Thr-Pro-Gln-Arg-Gly-Asp-Val-gamma-Abu-Asn-Asp-Gln-Glu-Glu-Thr-Thr-Gly-Val-Val-Ser-Thr-Pro-Leu-Ile-Arg-Asn-Gly-OH was designed to mimic the discontinuous epitope of the HLA-DQ molecule that might interact with CD4. The bridged peptide revealed distinct suppressory effect in the humoral immune response. This result supports our suggestion that the 164-172 region of the HLA-DQ molecule may enhance its interactions with coreceptors, possibly with CD4.

scholarly journals Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole Bearing Pyridine Moiety

2019 ◽  
pp. 300-307
Author(s):  
Asma D. Ambekari ◽  
Shrinivas K. Mohite
Keyword(s):  
Antimicrobial Activity ◽  
Mass Spectra ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Pyridine Moiety ◽  
Anti Inflammatory ◽  
Physicochemical Data ◽  
Synthesis And Biological Evaluation

Series of novel substituted Synthesis of N-{[5-(substituted)-1,3,4-oxadiazole-2-yl] carbamothioyl} derivatives containing 1,3,4-oxadiazole moiety were synthesized by microwave as a green chemistry method and conventional method by using pyridine 3- carboxylic acid as a starting material. The structures of the synthesized compounds were characterized by physicochemical data, IR, Mass spectra and 1HNMR. All the newly synthesized compound screened for their antimicrobial and In-vivo and In-vitro Anti-inflammatory studies. Anti-inflammatory studies revealed that compound 4f showed significant in-vivo and in-vitro anti-inflammatory activity as well potent antimicrobial activity.

scholarly journals Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long Tang ◽  
Jianchun Jiang ◽  
Guoqiang Song ◽  
Yajing Wang ◽  
Ziheng Zhuang ◽  
...  
Keyword(s):  
Small Molecules ◽  
Inhibitory Activity ◽  
Structural Modification ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
H Nmr ◽  
Lead Compounds ◽  
Activity Test ◽  
Synthesis And Biological Evaluation ◽  
C Nmr

AbstractA series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.

scholarly journals Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259008
Author(s):  
Leandro da Costa Clementino ◽  
Guilherme Felipe Santos Fernandes ◽  
Igor Muccilo Prokopczyk ◽  
Wilquer Castro Laurindo ◽  
Danyelle Toyama ◽  
...  
Keyword(s):  
Parasite Burden ◽  
Peritoneal Macrophages ◽  
Biological Evaluation ◽  
Antileishmanial Activity ◽  
Dual Effect ◽  
Design Synthesis ◽  
Murine Peritoneal Macrophages ◽  
Synthesis And Biological Evaluation

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

scholarly journals Hemiasterlin analogues incorporating an aromatic, and heterocyclic type C-terminus: design, synthesis and biological evaluation

2014 ◽  
Vol 18 (2) ◽  
pp. 357-373 ◽  
Author(s):  
Giordano Lesma ◽  
Alessandro Sacchetti ◽  
Rouli Bai ◽  
Giuseppe Basso ◽  
Roberta Bortolozzi ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Design Synthesis ◽  
C Terminus ◽  
Type C ◽  
Synthesis And Biological Evaluation
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