A stereoselective approach to peptidomimetic BACE1 inhibitors

Butini, Stefania; Gabellieri, Emanuele; Brindisi, Margherita; Giovani, Simone; Maramai, Samuele; Kshirsagar, Giridhar; Guarino, Egeria; Brogi, Simone; Pietra, Valeria La; Giustiniano, Mariateresa; Marinelli, Luciana; Novellino, Ettore; Campiani, Giuseppe; Cappelli, Andrea

doi:10.1016/j.ejmech.2013.09.056

Cited by 16 publications

(8 citation statements)

References 31 publications

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“…Subsequently the small 4 kilodalton of amyloid-A β 1-40 and A β 1-42 is generated by sequential β and γ -secretase cleavage of APP. Hence, the BACE1 has been recognized as a drug target for curing AD in many studies [16–18]. …”

Section: Introductionmentioning

confidence: 99%

In SilicoDesign of BACE1 Inhibitor for Alzheimer’s Disease by Traditional Chinese Medicine

Huang

Lee

Chen

2014

BioMed Research International

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The β-site APP cleaving enzyme 1 (BACE1) is an important target for causing Alzheimer's disease (AD), due to the brain deposition peptide amyloid beta (Aβ) require cleavages of amyloid precursor protein (APP) by BACE1 and γ-secretase, but treatments of AD still have side effect in recent therapy. This study utilizes the world largest traditional Chinese medicine (TCM) database and database screening to provide potential BACE1 inhibited compound. Molecular dynamics (MD) simulation was carried out to observe the dynamics structure after ligand binding. We found that Triptofordin B1 has less toxicity than pyrimidine analogue, which has more potent binding affinity with BACE1. For trajectory analysis, all conformations are tending to be stable during 5000 ps simulation time. In dynamic protein validation, the residues of binding region are still stable after MD simulation. For snapshot comparison, we found that Triptofordin B1 could reduce the binding cavity; the results reveal that Triptofordin B1 could bind to BACE1 and better than control, which could be used as potential lead drug to design novel BACE1 inhibitor for AD therapy.

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Section: Introductionmentioning

confidence: 99%

In SilicoDesign of BACE1 Inhibitor for Alzheimer’s Disease by Traditional Chinese Medicine

Huang

Lee

Chen

2014

BioMed Research International

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“…In addition, according to a computational study, the π–π stacking interaction between the phenyl-imino group and Phe108 added stability with the enzyme [ 34 ]. Butini and Kawai also obtained two series of BACE1 inhibitors, respectively, and the best compounds 14 , 15 of each series, shown in Figure 4 , exhibited IC 50 values of 12.8 and 2.3 μM [ 36 , 37 ]. The interaction between BACE1 and the piperazine ring is also shown in Figure 4 [ 34 ].…”

Section: Bace1 Inhibitors With Piperazine Structurementioning

confidence: 99%

Development and Structural Modification of BACE1 Inhibitors

Dong

et al. 2016

Molecules

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder which usually occurs in the elderly. The accumulation of β-amyloid and the formation of neurofibrillary tangles are considered as the main pathogenies of AD. Research suggests that β-secretase 1 (BACE1) plays an important role in the formation of β-amyloid. Discovery of new BACE1 inhibitors has become a significant method to slow down the progression of AD or even cure this kind of disease. This review summarizes the different types and the structural modification of these new BACE1 inhibitors.

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“…Thus, an inhibitor of BACE1 would prevent A production at the initial processing step, and could be a promising anti-AD drug [2][3][4][5][6][7][8] . Inhibition of BACE1 is expected to be clinically feasible, since BACE1 null mice proved viable with few phenotypical abnormalities.…”

Section: Introductionmentioning

confidence: 99%