Computer Modeling-Assisted Design And Synthesis Of Flavonols Derivatives As Proteasome Inhibitors

Planta Medica ◽  
2016 ◽  
Vol 82 (05) ◽  
Author(s):  
KY Orabi ◽  
MS Abaza ◽  
KA ElSayed ◽  
AY Elnagar ◽  
SI Faggal ◽  
...  
2007 ◽  
Vol 17 (4) ◽  
pp. 1102-1106 ◽  
Author(s):  
Yiqiu Fu ◽  
Bo Xu ◽  
Xiaomin Zou ◽  
Chao Ma ◽  
Xiaoming Yang ◽  
...  

2012 ◽  
Vol 22 (8) ◽  
pp. 2772-2774 ◽  
Author(s):  
Kai Xu ◽  
Zhiyan Xiao ◽  
Yan Bo Tang ◽  
Li Huang ◽  
Chin-Ho Chen ◽  
...  

2020 ◽  
Vol 1 (5) ◽  
pp. 305-332
Author(s):  
Grace E. Hubbell ◽  
Jetze J. Tepe

The 20S proteasome is a valuable target for the treatment of a number of diseases including cancer, neurodegenerative disease, and parasitic infection.


1982 ◽  
Vol 60 (8) ◽  
pp. 1019-1029 ◽  
Author(s):  
Patrice C. Belanger ◽  
Claude Dufresne ◽  
John Scheigetz ◽  
Robert N. Young ◽  
James P. Springer ◽  
...  

A model for the active conformation of methionine-enkephalin containing a β-turn was derived from computer modeling. Using a trans-perhydronaphthalene as a structural template and a mimic of the β-turn, target compounds were designed and synthesized. Thus, a key intermediate, trans-3-oxo-5β-formamidomethyl-8a-phenylmethylperhydronaphthalene, was prepared by two different routes from cyclohexanone.The addition of a methionine-like side-chain to this key intermediate was best achieved by a reaction with the anion of methyl 2-trimethylsilyl-4-methylthiobutanoate. This led to the preparation of an exo-tetrasubstituted double bond in high yield. Subsequent addition of tyrosine through coupling with the 5β-aminomethyl group provided the desired perhydronaphthalene mimics of met-enkaphalin.


Author(s):  
W. Allen Shannon ◽  
José A. Serrano ◽  
Hannah L. Wasserkrug ◽  
Anna A. Serrano ◽  
Arnold M. Seligman

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.


Author(s):  
Mehmet Sarikaya ◽  
Ilhan A. Aksay

Biomimetics involves investigation of structure, function, and methods of synthesis of biological composite materials. The goal is to apply this information to the design and synthesis of materials for engineering applications.Properties of engineering materials are structure sensitive through the whole spectrum of dimensions from nanometer to macro scale. The goal in designing and processing of technological materials, therefore, is to control microstructural evolution at each of these dimensions so as to achieve predictable physical and chemical properties. Control at each successive level of dimension, however, is a major challenge as is the retention of integrity between successive levels. Engineering materials are rarely fabricated to achieve more than a few of the desired properties and the synthesis techniques usually involve high temperature or low pressure conditions that are energy inefficient and environmentally damaging.In contrast to human-made materials, organisms synthesize composites whose intricate structures are more controlled at each scale and hierarchical order.


2005 ◽  
Vol 41 ◽  
pp. 205-218
Author(s):  
Constantine S. Mitsiades ◽  
Nicholas Mitsiades ◽  
Teru Hideshima ◽  
Paul G. Richardson ◽  
Kenneth C. Anderson

The ubiquitin–proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
B Kang ◽  
YJ Jung ◽  
R Jeon
Keyword(s):  

2013 ◽  
Vol 61 (S 01) ◽  
Author(s):  
CJ Beller ◽  
I Baxter ◽  
K Kallenbach ◽  
T Mesana ◽  
M Labrosse

1990 ◽  
Vol 29 (04) ◽  
pp. 282-288 ◽  
Author(s):  
A. van Oosterom

AbstractThis paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed.


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