Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases

• Published in: Xenobiotica Vol. 50; no. 3; pp. 261 - 269
• Main Authors: Mizoi, Kenta, Takahashi, Masato, Sakai, Sachiko, Ogihara, Takuo, Haba, Masami, Hosokawa, Masakiyo
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.03.2020
• Subjects: Activation, Metabolic; atorvastatin; Atorvastatin - metabolism; Carboxylesterase; Carboxylic Ester Hydrolases; Hydrolases - metabolism; metabolic activation; Microsomes, Liver - metabolism; prodrug; Prodrugs; Structure-Activity Relationship; Substrate Specificity; prodrug; Carboxylesterase; atorvastatin; structure-activity relationship; metabolic activation

1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only...