Acute animal toxicity and genotoxicity of obliquumol, a potential new framework antifungal compound isolated from Ptaeroxylon obliquum (Rutaceae) leaf extracts

Abstract

Obliquumol (12-O-acetylptaeroxylinol) isolated from Ptaeroxylon obliquum leaves has excellent antifungal activity and low cellular toxicity. As a next step in the potential development of a framework antifungal product, the present work investigated the acute animal toxicity of obliquumol according to OECD 423 guidelines. Furthermore, the genotoxicity of P. obliquum acetone leaf extracts, fractions (hexane, chloroform and 30 % H2O in MeOH) and isolated compounds (obliquumol and a mixture of lupeol and β-amyrin) was determined using Ames test. . A single dose of obliquumol was orally administered to mice at levels of 50, 300 and 2000 mg/kg and observed for 14 days. The three S. typhimurium tester strains TA 98, TA 100 and TA 102 were used without metabolic activation to determine the genotoxicity. Even at the highest dose of obliquumol, the mass, behaviour and food intake of the animals were not affected. Gross necropsy and histopathological analysis on organs indicated hardly any effects. No samples had genotoxic activity against the S. typhimurium strains tested. Obliquumol had an LD50 >2000 mg/kg since there were no mortalities after 14 days. This encourages the possible development of a new class of antifungal compounds from the obliquumol framework.