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

Omobolanle J. Jesumoroti; Richard M. Beteck; Lesetja J. Legoabe

doi:10.1055/a-1349-1256

Drug Research, Inhaltsverzeichnis

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

Omobolanle J. Jesumoroti

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

,

Richard M. Beteck

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

,

Lesetja J. Legoabe

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

› Institutsangaben

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].

Graphical Abstract.

Key words

sleeping sickness - 2-quinazolinone - hit - antitrypanosomal - cross screening

Volltext

Referenzen

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