| Autor: |
Hafez DE; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt., Dubiel M; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., La Spada G; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy., Catto M; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Bari, Italy., Reiner-Link D; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Syu YT; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan., Abdel-Halim M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt., Hwang TL; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.; Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan., Stark H; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Abadi AH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt. |
| Abstrakt: |
Neurodegenerative diseases such as Alzheimer's disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact with different biological targets relevant to the diseases, might offer an improved therapeutic alternative than using the traditional "one-target, one-molecule" approach. Herein, we describe new benzothiazole-based derivatives as a privileged scaffold for histamine H 3 receptor ligands (H 3 R). The most affine compound, the 3-(azepan-1-yl)propyloxy-linked benzothiazole derivative 4b, displayed a K i value of 0.012 μM. The multitargeting potential of these H 3 R ligands towards AChE, BuChE and MAO-B enzymes was evaluated to yield compound 3s (pyrrolidin-1-yl-(6-((5-(pyrrolidin-1-yl)pentyl)oxy)benzo[d]thiazol-2-yl)methanone) as the most promising MTDL with a K i value of 0.036 μM at H 3 R and IC 50 values of 6.7 µM, 2.35 µM, and 1.6 µM towards AChE, BuChE, and MAO-B, respectively. These findings suggest that compound 3s can be a lead structure for developing new multi-targeting anti-AD agents. |
