2. Academic Validation
  3. Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease

Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease

  • J Nat Prod. 2007 Sep;70(9):1397-405. doi: 10.1021/np060092r.
Mark Hamann 1,  Diana Alonso,  Ester Martín-Aparicio,  Ana Fuertes,  M José Pérez-Puerto,  Ana Castro,  Susana Morales,  María Luisa Navarro,  María Del Monte-Millán,  Miguel Medina,  Hari Pennaka,  Akula Balaiah,  Jiangnan Peng,  Jennifer Cook,  Subagus Wahyuono,  Ana Martínez
Affiliations

Affiliation

  • 1 Department of Pharmacognosy, Pharacology, Chemistry and Biochemistry, School of Pharmacy, University of Mississippi, Mississippi 38677, USA.
PMID: 17708655 DOI: 10.1021/np060092r
Abstract

Manzamine A and related derivatives isolated from a common Indonesian Sponge, Acanthostrongylophora, have been identified as a new class of GSK-3beta inhibitors. The semisynthesis of new analogues and the first structure-activity relationship studies with GSK-3beta are also reported. Moreover, manzamine A proved to be effective in decreasing tau hyperphosphorylation in human neuroblastoma cell lines, a demonstration of its ability to enter cells and interfere with tau pathology. Inhibition studies of manzamine A against a selected panel of five different kinases related to GSK-3beta, specifically CDK-1, PKA, CDK-5, MAPK, and GSK-3alpha, show the specific inhibition of manzamine A on GSK-3beta and CDK-5, the two kinases involved in tau pathological hyperphosphorylation. These results suggest that manzamine A constitutes a promising scaffold from which more potent and selective GSK-3 inhibitors could be designed as potential therapeutic agents for Alzheimer's disease.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z