Acute Toxicity, Bioactivity, and Enantioselective Behavior with Tissue Distribution in Rabbits of Myclobutanil Enantiomers. Issue 12 (21st July 2014)

• Record Type: Journal Article
• Authors: Sun, Mingjing; Liu, Donghui; Qiu, Xinxu; Zhou, Qian; Shen, Zhigang; Wang, Peng; Zhou, Zhiqiang
• Is Part Of: Chirality. Volume 26:Issue 12(2014:Dec.)
• Page Start: 784
• Page End: 789
• Publication Date: 2014-07-21
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22353
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>The <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enantioselective</named-content> bioactivity against pathogens <italic>(Cercospora arachidicola, Fulvia fulva, </italic> and <italic>Phytophthora infestans</italic>) and acute toxicity to <italic>Daphnia magna</italic> of the fungicide myclobutanil enantiomers were studied. The (+)‐enantiomer in an <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">antimicrobial activity</named-content> test was about 1.79–1.96 times more active than the (–)‐enantiomer. In the toxicity assay, the calculated 24‐h LC<sub>50</sub> values of the (–)‐form, rac‐form and (+)‐form were 16.88, 13.17, and 11.91 mg/L, and the 48‐h LC<sub>50</sub> values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)‐myclobutanil was more toxic. Meanwhile, the <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enantioselective</named-content> metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)‐enantiomer was 1.68‐fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)‐enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low‐activity (–)‐myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. <italic>Chirality 26:784–789, 2014.</italic> © 2014 Wiley Periodicals, Inc.</p> </abstract>