Anti-Trypanosomal and Antimalarial Properties of Tetralone Derivatives and Structurally Related Benzocycloalkanones

• Main Authors: Richard M. Beteck, Lesetja J. Legoabe, Michelle Isaacs, Setshaba D. Khanye, Dustin Laming, Heinrich C. Hoppe
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Medicina
• Subjects: sleeping sickness; malaria; hit optimization; anti-trypanosomal; anti-malarial; tetralone; benzocycloalkanone
• Online Access: https://www.mdpi.com/1010-660X/55/5/206

<i>Background and objectives</i>: Sleeping sickness and malaria alike are insect-borne protozoan diseases that share overlapping endemic areas in sub-Saharan Africa. The causative agent for malaria has developed resistance against all currently deployed anti-malarial agents. In the case of sleeping sickness, the currently deployed therapeutic options are limited in efficacy and activity spectra, and there are very few drug candidates in the development pipeline. Thus, there is a need to search for new drug molecules with a novel mode of actions. <i>Materials and Methods</i>: In the current study, an in vitro screening of a library of tetralone derivatives and related benzocycloalkanones was effected against <i>T. b. brucei</i> and <i>P. falciparum</i>. <i>Results</i>: Several hits with low micromolar activity (0.4&#8722;8 &#181;M) against <i>T. b. brucei</i> were identified. <i>Conclusions</i>: The identified hits have a low molecular weight (&lt;280 Da), a low total polar surface area (&lt;50 Å&#178;), and a defined structure activity relationship, which all make them potential starting points for further hit optimization studies.