Bioorganic and Medicinal Chemistry Letters p. 537 - 541 (2017)
Update date:2022-09-26
Topics:
Gordhan, Heeren M.
Patrick, Stephen L.
Swasy, Maria I.
Hackler, Amber L.
Anayee, Mark
Golden, Jennifer E.
Morris, James C.
Whitehead, Daniel C.
Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold. With the exception of one methyl ester derivative, these modifications ablated or blunted the potent TbHK1 inhibition of the parent scaffold. Nonetheless, a few of the methyl ester derivatives still exhibited trypanocidal effects with single-digit micromolar or high nanomolar EC50values.
View MoreTIANJIN DONGRUXIANG MINERALS MARKETING CO.,LTD
Contact:22-58516360
Address:tianjin
Qingzhou Baibang import and export co.,Ltd
Contact:+86-536-3265899
Address:No.338, Tuoshan Road
Shanghai Send Pharmaceutical Technology Co., Ltd.
website:http://www.shsendpharma.com
Contact:021-58088081, +8613585868794
Address::Room A601, Building 1,NO. 800 Qingdai Road Pudong District Shanghai,China
Luzhou North Chemical Co., Ltd.
Contact:+86-830-2796784;+86-830-2796776
Address:Gaoba, Longmatan District, Luzhou, Sichuan Province
Contact:+86-28-88523492
Address:714rooms of Time Square, Pujiang County
Doi:10.1023/A:1013111016841
(2001)Doi:10.1016/S0040-4039(00)01282-X
(2000)Doi:10.1021/ol061742l
(2006)Doi:10.1080/07328300008544127
(2000)Doi:10.1021/ja01140a025
(1952)Doi:10.3390/50200179
(2000)