Beteck Richard M, Legoabe Lesetje J, Isaacs Michelle, Hoppe Heinrich C
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, South Africa.
Drug Res (Stuttg). 2019 Jun;69(6):337-341. doi: 10.1055/a-0775-0737. Epub 2018 Nov 16.
Human African trypanosomiasis is a neglected infectious disease that affects mostly people living in the rural areas of Africa. Current treatment options are limited to just four drugs that have been in use of four to nine decades. The life-threatening toxic side-effects associated with the use of these drugs are disconcerting. Poor efficacy, low oral bioavailability, and high cost are other shortcomings of current HAT treatments. Evaluating the potentials of known hits for other therapeutic areas may be a fast and convenient method to discover new hit compounds against alternative targets. A library of 34 known indanone based chalcones was screened against T.b. brucei and nine potent hits, having IC values between 0.5-8.9 µM, were found. The SAR studies of this series could provide useful information in guiding future exploration of this class of compounds in search of more potent, safe, and low cost anti-trypanosomal agents. Graphical Abstract.
人类非洲锥虫病是一种被忽视的传染病，主要影响生活在非洲农村地区的人们。目前的治疗选择仅限于四种已使用了四至九十年的药物。使用这些药物所带来的危及生命的毒副作用令人不安。疗效不佳、口服生物利用度低和成本高是当前人类非洲锥虫病治疗方法的其他缺点。评估已知活性化合物在其他治疗领域的潜力可能是发现针对替代靶点的新活性化合物的快速便捷方法。针对布氏锥虫对一个包含34种已知茚满酮基查尔酮的文库进行了筛选，发现了9种活性较强的化合物，其IC值在0.5 - 8.9 μM之间。该系列的构效关系研究可为今后探索这类化合物以寻找更有效、安全且低成本的抗锥虫药物提供有用信息。图形摘要。
