Bioorganic and Medicinal Chemistry p. 1143 - 1152 (2017)
Update date:2022-08-10
Topics:
Hroch, Lukas
Guest, Patrick
Benek, Ondrej
Soukup, Ondrej
Janockova, Jana
Dolezal, Rafael
Kuca, Kamil
Aitken, Laura
Smith, Terry K.
Gunn-Moore, Frank
Zala, Dominykas
Ramsay, Rona R.
Musilek, Kamil
Alzheimer's disease (AD) is a neurodegenerative disorder associated with an excessive accumulation of amyloid-beta peptide (Aβ). Based on the multifactorial nature of AD, preparation of multi-target-directed ligands presents a viable option to address more pathological events at one time. A novel class of asymmetrical disubstituted indolyl thioureas have been designed and synthesized to interact with monoamine oxidase (MAO) and/or amyloid-binding alcohol dehydrogenase (ABAD). The design combines the features of known MAO inhibitors scaffolds (e.g. rasagiline or ladostigil) and a frentizole moiety with potential to interact with ABAD. Evaluation against MAO identified several compounds that inhibited in the low to moderate micromolar range. The most promising compound (19) inhibited human MAO-A and MAO-B with IC50values of 6.34 μM and 0.30 μM, respectively. ABAD activity evaluation did not show any highly potent compound, but the compound series allowed identification of structural features to assist the future development of ABAD inhibitors. Finally, several of the compounds were found to be potent inhibitors of horseradish peroxidase (HRP), preventing the use of the Amplex Red assay to detect hydrogen peroxide produced by MAO, highlighting the need for serious precautions when using an enzyme-coupled assay.
View MoreBaoding City Light Industry And Textiles Imp.& Exp. Corp. Chemical Department.
Contact:86-312-3262436
Address:NO.658 CHAOYANG SOUTH STREET,BAODING CITY HEBEI CHINA
SEA BRGIHT INDUSTRY CO.,LIMITED
Contact:0086 755 8622 3990
Address:Rm 17B3,GuangCaiXinTianDi Bldg,GuiMiao Rd,NanShan District,Shenzhen,China
Zibo Ocean International Trade Co.,Ltd
Contact:+86 533 5160706
Address:1117, Hongtai Bld., Songling rd, Zichuan,Zibo,Shandong,China
Contact:0091-265-2313036
Address:311, ATLANTIS HEIGHTS SARABHAI MAIN ROAD,VADIWADI ,VADODARA
Taizhou Crene Biotechnology co.ltd
Contact:86-576-88813233 88205808
Address:Economic Developed Zone of Taizhou Zhejiang China
Doi:10.1021/jp040366o
(2004)Doi:10.1016/S0957-4166(02)00650-X
(2002)Doi:10.1016/0009-3084(94)90059-0
(1994)Doi:10.1021/acs.orglett.1c00573
(2021)Doi:10.1007/BF00764458
(1989)Doi:10.1007/s11164-016-2587-7
(2016)