Enantioselective Degradation of (2RS, 3RS)‐Paclobutrazol in Rat Liver Microsomes. Issue 5 (28th March 2015)

• Record Type: Journal Article
• Authors: Wu, Shuchun; Yu, Miao; Zhang, Hu.; Han, Jianzhong; Qian, Mingrong
• Is Part Of: Chirality. Volume 27:Issue 5(2015)
• Page Start: 344
• Page End: 348
• Publication Date: 2015-03-28
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22440
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Paclobutrazol, with two stereogenic centers, but gives only (2<italic>R</italic>, 3<italic>R</italic>) and (2<italic>S</italic>, 3<italic>S</italic>)‐enantiomers because of steric‐hindrance effects, is an important <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">plant growth regulator</named-content> in agriculture and horticulture. <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">Enantioselective</named-content> degradation of paclobutrazol was investigated in rat liver microsomes in vitro. The degradation kinetics and the enantiomer fraction were determined using a Lux Cellulose‐1 chiral column on a reverse‐phase liquid chromatography–tandem <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">mass spectrometry</named-content> system. The <italic>t</italic><sub>1/2</sub> of (2<italic>R</italic>, 3<italic>R</italic>)‐paclobutrazol is 18.60 min, while the <italic>t</italic><sub>1/2</sub> of (2<italic>S</italic>, 3<italic>S</italic>)‐paclobutrazol is 10.93 min. Such consequences clearly indicated that the degradation of paclobutrazol in rat liver microsomes was <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">stereoselective</named-content> and the degradation rate of (2<italic>S</italic>, 3<italic>S</italic>)‐paclobutrazol was much faster than (2<italic>R</italic>, 3<italic>R</italic>)‐paclobutrazol. In addition, significant differences between the two enantiomers were also observed in enzyme kinetic parameters. The <italic>V<sub>max</sub></italic> of (2<italic>S</italic>, 3<italic>S</italic>)‐paclobutrazol was more than 2‐fold of (2<italic>R</italic>, 3<italic>R</italic>)‐paclobutrazol and the Cl<sub>int</sub> of (2<italic>S</italic>, 3<italic>S</italic>)‐paclobutrazol was higher than that of (2<italic>R</italic>, 3<italic>R</italic>)‐paclobutrazol after incubation in rat liver microsomes. These results may have potential implications for better environmental and ecological <named-content content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">risk assessment</named-content> for paclobutrazol. <italic>Chirality 27:344–348, 2015</italic>. © 2015 Wiley Periodicals, Inc.</p> </abstract>