Drug Res (Stuttg) 2021; 71(06): 335-340
DOI: 10.1055/a-1349-1256
Original Article

In-vitro Anti-trypanosomal and Cytotoxicity Evaluation of 3-methyl-3,4-dihydroquinazolin-2(1H)-one Derivatives

1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Richard M. Beteck
1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Lesetja J. Legoabe
1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
› Author Affiliations
Funding: The bioassay component of the project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package awarded to Prof. Heinrich Hoppe, Rhodes University. The authors are grateful to North-West University for financial support.

Abstract

Sleeping sickness, caused by trypanosomes, is a debilitating, neglected tropical disease wherein current treatments suffer from several drawbacks such as toxicity, low activity, and poor pharmacokinetic properties, and hence the need for alternative treatment is apparent. To this effect, we screened in vitro a library of 2-quinazolinone derivatives for antitrypanosomal activity against T.b. brucei and cytotoxicity against HeLa cells. Seven compounds having no overt cytotoxicity against HeLa cells exhibited antitrypanosomal activity in the range of 0.093–45 µM were identified. The activity data suggests that the antitrypanosomal activity of this compound class is amenable to substituents at N1 and C6 positions. Compound 14 having a molecular weight of 238Da, ClogP value of 1 and a total polar surface area of 49 was identified as the most active, exhibiting an IC50 value of 0.093 µM [Graphical Abstract].

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Graphical Abstract.

Supplementary Material



Publication History

Received: 20 November 2020

Accepted: 05 January 2021

Publication Date:
03 February 2021 (online)

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