Abstract
One of the characteristics of Alzheimer's disease (AD) that hinders the discovery of effective disease-modifying therapies is the multifactorial nature of its etiopathology. To circumvent this drawback, the use of multi-target-directed ligands (MTDLs) has recently been proposed as a means of simultaneously hitting several targets involved in the development of the AD syndrome. In this paper, a new class of MTDLs based on a polyamine - quinone skeleton, whose lead (memoquin, 2) showed promising properties in preclinical investigations (Cavalli et al. Angew. Chem., Int. Ed. 2007, 46, 3689-3692), is described. 3-29 were tested in vitro against a number of isolated AD-related targets, namely, AChE and BChE, and Aβ aggregation (both AChE-mediated and self-induced). Furthermore, the ability of the compounds to counteract the oxidative stress in a human neuronal-like cellular system (SH-SY5Y cells) was assayed, in both the presence and absence of NQO1, an enzyme able to generate and maintain the reduced form of quinone.
| Original language | English |
|---|---|
| Pages (from-to) | 4882-4897 |
| Number of pages | 16 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 50 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - Oct 20 2007 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease. / Bolognesi, Maria Laura; Banzi, Rita; Bartolini, Manuela; Cavalli, Andrea; Tarozzi, Andrea; Andrisano, Vincenza; Minarini, Anna; Rosini, Michela; Tumiatti, Vincenzo; Bergamini, Christian; Fato, Romana; Lenaz, Giorgio; Hrelia, Patrizia; Cattaneo, Antonino; Recanatini, Maurizio; Melchiorre, Carlo.
In: Journal of Medicinal Chemistry, Vol. 50, No. 20, 20.10.2007, p. 4882-4897.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease
AU - Bolognesi, Maria Laura
AU - Banzi, Rita
AU - Bartolini, Manuela
AU - Cavalli, Andrea
AU - Tarozzi, Andrea
AU - Andrisano, Vincenza
AU - Minarini, Anna
AU - Rosini, Michela
AU - Tumiatti, Vincenzo
AU - Bergamini, Christian
AU - Fato, Romana
AU - Lenaz, Giorgio
AU - Hrelia, Patrizia
AU - Cattaneo, Antonino
AU - Recanatini, Maurizio
AU - Melchiorre, Carlo
PY - 2007/10/20
Y1 - 2007/10/20
N2 - One of the characteristics of Alzheimer's disease (AD) that hinders the discovery of effective disease-modifying therapies is the multifactorial nature of its etiopathology. To circumvent this drawback, the use of multi-target-directed ligands (MTDLs) has recently been proposed as a means of simultaneously hitting several targets involved in the development of the AD syndrome. In this paper, a new class of MTDLs based on a polyamine - quinone skeleton, whose lead (memoquin, 2) showed promising properties in preclinical investigations (Cavalli et al. Angew. Chem., Int. Ed. 2007, 46, 3689-3692), is described. 3-29 were tested in vitro against a number of isolated AD-related targets, namely, AChE and BChE, and Aβ aggregation (both AChE-mediated and self-induced). Furthermore, the ability of the compounds to counteract the oxidative stress in a human neuronal-like cellular system (SH-SY5Y cells) was assayed, in both the presence and absence of NQO1, an enzyme able to generate and maintain the reduced form of quinone.
AB - One of the characteristics of Alzheimer's disease (AD) that hinders the discovery of effective disease-modifying therapies is the multifactorial nature of its etiopathology. To circumvent this drawback, the use of multi-target-directed ligands (MTDLs) has recently been proposed as a means of simultaneously hitting several targets involved in the development of the AD syndrome. In this paper, a new class of MTDLs based on a polyamine - quinone skeleton, whose lead (memoquin, 2) showed promising properties in preclinical investigations (Cavalli et al. Angew. Chem., Int. Ed. 2007, 46, 3689-3692), is described. 3-29 were tested in vitro against a number of isolated AD-related targets, namely, AChE and BChE, and Aβ aggregation (both AChE-mediated and self-induced). Furthermore, the ability of the compounds to counteract the oxidative stress in a human neuronal-like cellular system (SH-SY5Y cells) was assayed, in both the presence and absence of NQO1, an enzyme able to generate and maintain the reduced form of quinone.
UR - http://www.scopus.com/inward/record.url?scp=34948904272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948904272&partnerID=8YFLogxK
U2 - 10.1021/jm070559a
DO - 10.1021/jm070559a
M3 - Article
C2 - 17850125
AN - SCOPUS:34948904272
VL - 50
SP - 4882
EP - 4897
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 20
ER -