Abstract
In the current work a new class of novel benzothiazole-hydrazone derivatives was designed and synthesized as hMAO-B inhibitors. Structures of the obtained compounds (3a–3j) were characterized by IR, 1H-NMR, 13C-NMR, and HRMS spectroscopic methods. The inhibitory activity of compounds (3a–3j) against hMAO-A and hMAO-B enzymes was evaluated by using an in vitro fluorometric method. According to activity results, some of the synthesized compounds displayed selective and significant hMAO-B enzyme inhibitor activity. Compound 3e was the most active derivative in the series with an IC50 value of 0.060 µM. Furthermore, cytotoxicity of compound 3e was investigated and found to be non-cytotoxic. Absorption, distribution, metabolism, and excretion (ADME) and blood-brain barrier (BBB) permeability predictions were performed for all compounds. It was determined that these compounds may have a good pharmacokinetic profiles. Bınding modes between the most active compound 3e and the hMAO-B enzyme were analyzed by docking studies. It was observed that there is a strong interaction between compound 3e and enzyme active site.
Highlights
Design and Synthesis of New BenzothiazoleSinem Ilgın 1 , Derya Osmaniye 2,3 , Serkan Levent 2,3 , Begüm Nurpelin Sağlık 2,3 , Ulviye Acar Çevik 2,3 , Betül Kaya Çavuşoğlu 2 , Yusuf Özkay 2,3, * and Zafer Asım Kaplancıklı 2
Monoamine oxidase (MAO) is an important flavoenzyme existing in the outer mitochondrial membrane of neuronal, glial, and many other cells, and is responsible for the oxidative deamination of amines in the brain, as well as peripheral tissues to regulate their level
The compounds 3a–3j were synthesized as summarized in Scheme 1
Summary
Sinem Ilgın 1 , Derya Osmaniye 2,3 , Serkan Levent 2,3 , Begüm Nurpelin Sağlık 2,3 , Ulviye Acar Çevik 2,3 , Betül Kaya Çavuşoğlu 2 , Yusuf Özkay 2,3, * and Zafer Asım Kaplancıklı 2. Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470, Eskişehir, Turkey. Received: 15 November 2017; Accepted: 8 December 2017; Published: 9 December 2017
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have