5147-17-1Relevant articles and documents
Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
, (2021/10/29)
Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
Structure-Activity Relationships of cyclo(l -Tyrosyl- l -tyrosine) Derivatives Binding to Mycobacterium tuberculosis CYP121: Iodinated Analogues Promote Shift to High-Spin Adduct
Rajput, Sunnia,McLean, Kirsty J.,Poddar, Harshwardhan,Selvam, Irwin R.,Nagalingam, Gayathri,Triccas, James A.,Levy, Colin W.,Munro, Andrew W.,Hutton, Craig A.
, p. 9792 - 9805 (2019/11/13)
A series of analogues of cyclo(l-tyrosyl-l-tyrosine), the substrate of the Mycobacterium tuberculosis enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto cyclo(l-tyrosyl-l-tyrosine) results in sub-μM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme FeIII. The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds.
Anti-biofilm and anti-adherence properties of novel cyclic dipeptides against oral pathogens
Simon, Ga?lle,Bérubé, Christopher,Voyer, Normand,Grenier, Daniel
, p. 2323 - 2331 (2018/12/11)
Microorganisms embedded in a biofilm are significantly more resistant to antimicrobial agents and the defences of the human immune system, than their planktonic counterpart. Consequently, compounds that can inhibit biofilm formation are of great interest for novel therapeutics. In this study, a screening approach was used to identify novel cyclic dipeptides that have anti-biofilm activity against oral pathogens. Five new active compounds were identified that prevent biofilm formation by the cariogenic bacterium Streptococcus mutans and the pathogenic fungus Candida albicans. These compounds also inhibit the adherence of microorganisms to a hydroxylapatite surface. Further investigations were conducted on these compounds to establish the structure–activity relationship, and it was deduced that the common cleft pattern is required for these molecules to act effectively against biofilms.
Radical-Scavenging Antioxidant Cyclic Dipeptides and Silk Fibroin Biomaterials
Manchineella, Shivaprasad,Voshavar, Chandrashekhar,Govindaraju, Thimmaiah
, p. 4363 - 4369 (2017/08/23)
Cyclic dipeptide (CDP) based radical-scavenging antioxidant molecules have been developed through structure–activity screening of rationally designed symmetric and asymmetric aromatic molecules. The antioxidant efficiencies of the designed CDPs were evalu
Marine natural occurring 2,5-diketopiperazines: Isolation, synthesis and optical properties
Laville, Rmi,Nguyen, Thanh Binh,Moriou, Cline,Petek, Sylvain,Debitus, Ccile,Al-Mourabit, Ali
, p. 1351 - 1366 (2015/03/04)
Seven 2,5-diketopiperazines (DKPs) were isolated from the Fijian marine sponge Acanthella cavernosa. NMR and circular dichroism (CD) comparison with synthetic L-L DKPs allowed us to determine unambiguously the L-L absolute configuration of the natural DKPs. This work initiated the setting up of an optical properties database of natural DKPs, including specific rotation and CD.
Cyclo(D-Tyr-D-Phe): A new antibacterial, anticancer, and antioxidant cyclic dipeptide from Bacillus sp. N strain associated with a rhabditid entomopathogenic nematode
Nishanth Kumar,Dileep,Mohandas,Nambisan, Bala,Ca, Jayaprakas
, p. 173 - 185 (2014/03/21)
A new microbial cyclic dipeptide (diketopiperazine), cyclo(d-Tyr-d-Phe) was isolated for the first time from the ethyl acetate extract of fermented modified nutrient broth of Bacillus sp. N strain associated with rhabditid Entomopathogenic nematode. Antibacterial activity of the compound was determined by minimum inhibitory concentration and agar disc diffusion method against medically important bacteria and the compound recorded significant antibacterial against test bacteria. Highest activity was recorded against Staphylococcus epidermis (1 μg/ml) followed by Proteus mirabilis (2 μg/ml). The activity of cyclo(d-Tyr-d-Phe) against S. epidermis is better than chloramphenicol, the standard antibiotics. Cyclo(d-Tyr-d-Phe) recorded significant antitumor activity against A549 cells (IC50 value: 10 μM) and this compound recorded no cytotoxicity against factor signaling normal fibroblast cells up to 100 μM. Cyclo(d-Tyr-d-Phe) induced significant morphological changes and DNA fragmentation associated with apoptosis in A549 cells. Acridine orange/ethidium bromide stained cells indicated apoptosis induction by cyclo(d-Tyr-d-Phe). Flow cytometry analysis showed that the cyclo(d-Tyr-d-Phe) did not induce cell cycle arrest. Effector molecule of apoptosis such as caspase-3 was found activated in treated cells, suggesting apoptosis as the main mode of cell death. Antioxidant activity was evaluated by free radical scavenging and reducing power activity, and the compound recorded significant antioxidant activity. The free radical scavenging activity of cyclo(d-Tyr-d-Phe) is almost equal to that of butylated hydroxyanisole, the standard antioxidant agent. We also compared the biological activity of natural cyclo(d-Tyr-d-Phe) with synthetic cyclo(d-Tyr-d-Phe) and cyclo(l-Tyr-l-Phe). Natural and synthetic cyclo(d-Tyr-d-Phe) recorded similar pattern of activity. Although synthetic cyclo(l-Tyr-l-Phe) recorded lower activity. But in the case of reducing power activity, synthetic cyclo(l-Tyr-l-Phe) recorded significant activity than natural and synthetic cyclo(d-Tyr-d-Phe). The results of the present study reveals that cyclo(d-Tyr-d-Phe) is more bioactive than cyclo(l-Tyr-l-Phe). To the best of our knowledge, this is the first time that cyclo(d-Tyr-d-Phe) has been isolated from microbial natural source and also the antibacterial, anticancer, and antioxidant activity of cyclo(d-Tyr-d-Phe) is also reported for the first time. Copyright
Engineered transaminopeptidase, aminolysin-S for catalysis of peptide bond formation to give linear and cyclic dipeptides by one-pot reaction
Usuki, Hirokazu,Uesugi, Yoshiko,Arima, Jiro,Yamamoto, Yukihiro,Iwabuchi, Masaki,Hatanaka, Tadashi
supporting information; experimental part, p. 580 - 582 (2010/05/01)
Aminopeptidase from Streptomyces thermocyaneoviolaceus NBRC14271 was engineered into transaminopeptidase and used to catalyze an aminolysis reaction to give linear and cyclic dipeptides from cost-effective substrates such as the ester derivatives of amino
Synthesis of a small library of diketopiperazines as potential inhibitors of calpain
Zeng, Yibin,Li, Qingshan,Hanzlik, Robert P.,Aube, Jeffrey
, p. 3034 - 3038 (2007/10/03)
A small library of 2,5-diketopiperazines based on previously reported calpain inhibitors was synthesized. In addition, a concise total synthesis of the structurally related natural product phevalin (2) was accomplished. Despite literature reports that som
