In vitro Anti-Trypanosomal Activities of Indanone-Based Chalcones

Richard M. Beteck; Lesetje J. Legoabe; Michelle Isaacs; Heinrich C. Hoppe

doi:10.1055/a-0775-0737

Drug Research, Table of Contents

Drug Res (Stuttg) 2019; 69(06): 337-341
DOI: 10.1055/a-0775-0737

Original Article

In vitro Anti-Trypanosomal Activities of Indanone-Based Chalcones

Authors

Richard M. Beteck

¹Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
Lesetje J. Legoabe

¹Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
Michelle Isaacs

²Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, South Africa
Heinrich C. Hoppe

²Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, South Africa

³Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa

Abstract

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 IC₅₀ 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]

Graphical Abstract

Key words

indanones - chalcones - anti-trypanosomal - HTS - HAT

Full Text

References

References
1 http://www.who.int/neglected_diseases/diseases/en/ Accessed on 14.08.2017
2 Steverding D. The history of African trypanosomiasis. Parasites & Vectors 2008; 1: 3
3 Wang X, Inaok shows that they meet the a D, Shiba T. et al. Expression, purification, and crystallization of type 1 isocitrate dehydrogenase from Trypanosoma brucei brucei. Protein Expr Purif 2017; 138: 56-62
4 Gordhan H, Patrick S, Swasy M. et al. Evaluation of substituted ebselen derivatives as potential trypanocidal agents. Bioorg. Med. Chem. Lett 2017; 27: 537-541
5 Beig M, Oellien F, Garoff L. et al. Trypanothione reductase: A target protein for a combined in vitro and in silico screening approach. PLoS Negl Trop Dis 2015; 9: e0003773
6 Kuepfer I, Hhary E, Allan M. et al. Clinical presentation of T.b. rhodesiense sleeping sickness in second stage patients from Tanzania and Uganda. PLoS Negl Trop Dis 2011; 5: e968
7 Wamwiri F, Changasi R. tsetse flies (glossina) as vectors of human african trypanosomiasis: A review. Biomed Res. Int 2016; 2016; 1-8
8 Kennedy P. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 2013; 12: 186-194
9 http://www.who.int/mediacentre/factsheets/fs259/en/ Accessed on 14.08.2017
10 Tran H, Zheng Z, Wen X. et al. Synthesis and activity of nucleoside-based antiprotozoan compounds. Bioorg. Med. Chem 2017; 25: 2091-2104
11 Choi J, Cho Y, Shim E. et al. Web-based infectious disease surveillance systems and public health perspectives: A systematic review. BMC Public Health 2016; 16: 1238
12 Babokhov P, Sanyaolu A, Oyibo W. et al. A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis. Pathog. Glob. Health 2013; 107: 242-252
13 Malvy D, Chappuis F. Sleeping sickness. Clin Microbiol Infect 2011; 17: 986-995
14 Burri C. Chemotherapy against human African trypanosomiasis: Is there a road to success?. Parasito 2010; 137: 1987-1994
15 Pohlig G, Bernhard S, Blum J. et al. Efficacy and safety of pafuramidine versus pentamidine maleate for treatment of first stage sleeping sickness in a randomized, comparator-controlled, international phase 3 clinical trial. PLoS Negl Trop Dis 2016; 10: e0004363
16 Zhou B, Xing C. Diverse molecular targets for chalcones with varied bioactivities. Med Chem (Los Angeles) 2015; 5: 388-404
17 Hans RH, Guantai EM, Lategan C. et al. Synthesis, antimalarial and antitubercular activity of acetylenic chalcones. Bioorg Med Chem Lett 2010; 20: 942-944
18 Domínguez JN, de Domínguez NJ, Rodrigues J. et al. Synthesis and antimalarial activity of urenyl Bischalcone in vitro and in vivo. J Enzyme Inhib Med Chem 2013; 28: 1267-1273
19 Yadav N, Dixit SK, Bhattacharya A. et al. Antimalarial activity of newly synthesized chalcone derivatives in vitro. Chem Biol Drug Des 2012; 80: 340-347
20 Nel MS, Petzer A, Petzer JP. et al. 2-Benzylidene-1-indanone derivatives as inhibitors of monoamine oxidase. Bioorg Med Chem Lett 2016; 26: 4599-4605
21 Nel MS, Petzer A, Petzer JP. et al. 2-Heteroarylidene-1-indanone derivatives as inhibitors of monoamine Oxidase. Bioorg Chem 2016; 69: 20-28