{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:04:49Z","timestamp":1770509089183,"version":"3.49.0"},"reference-count":78,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T00:00:00Z","timestamp":1457395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundations of China","award":["81227802"],"award-info":[{"award-number":["81227802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A), as well as UDP-glucuronosyltransferases (UGTs) primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs\u2019 metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs) induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3\u2032 and C-4\u2032 positions, the configuration of C-3\u2032 and C-4\u2032, and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs.<\/jats:p>","DOI":"10.3390\/molecules21030314","type":"journal-article","created":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T10:14:25Z","timestamp":1457432065000},"page":"314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review"],"prefix":"10.3390","volume":"21","author":[{"given":"Wanghui","family":"Jing","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruilin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Du","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengqi","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiguo","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2032an Jiaotong University, No. 76, Yanta West Street, Xi\u2032an 710061, Shannxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0031-6997(24)01340-1","article-title":"Role of pharmacokinetics and metabolism in drug discovery and development","volume":"49","author":"Lin","year":"1997","journal-title":"Pharmacol. 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